Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treati...Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treating migraines through the use of network pharmacology and a rat migraine model.Methods:After identifying the active components of Horcha-6,the corresponding genes of the active components’target were obtained from the Universal Protein database,and a“compound-target-disease”network was constructed using Cytoscape 3.9.0 software.For the in vivo experiments,nitroglycerin was injected intraperitoneally into rats to create a migraine model.Pre-treatment with Horcha-6 was administered orally for 14 days,and rats were subjected to migraine-related behavior tests.RNA sequencing was performed to identify the gene expression regulated by Horcha-6 in the trigeminal nerve.Results:A total of 903 chemical components of Horcha-6 have been collected in the liquid chromatography with tandem mass spectrometry.We discovered 55 of the Horcha-6 bio-active components that were evaluated based on their Percent Human Oral Absorption(≥30%)and DL values(≥0.185)on the traditional Chinese medicine systems pharmacology database.The“compound-target-disease”network contained 163 intersection targets with the migraine state.Gene Ontology analysis indicated that these components significantly regulated the immune response,vascular function,oxidative stress,etc.When Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed,we observed that most of the target genes were significantly enriched in the inflammation and neuro-related signaling pathway,toll-like receptor signaling pathway,neuroactive ligand-receptor interaction,etc.These predictions were further demonstrated via in vivo animal model experiments.The RNA sequencing results showed that 41 genes were down-regulated(P<0.05)and 86 genes were up-regulated(P<0.05)in the Horcha-6 treated group compared with the untreated group.Those genes were mainly involved in neuromodulation,vascular function,and hormone metabolism.Conclusion:The 55 bio-active components in Horcha-6 regulate inflammation,hormone metabolism,and neurotransmitters and have potential as a therapy to treat migraines.展开更多
The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adapt...The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions.展开更多
High ce rvical spinal co rd injuries induce permanent neuromotor and autonomic deficits.These injuries impact both central respiratory and cardiovascular functions through modulation of the sympathetic nervous system....High ce rvical spinal co rd injuries induce permanent neuromotor and autonomic deficits.These injuries impact both central respiratory and cardiovascular functions through modulation of the sympathetic nervous system.So far,cardiovascular studies have focused on models of complete contusion or transection at the lower cervical and thoracic levels and diaphragm activity evaluations using invasive methods.The present study aimed to evaluate the impact of C2 hemisection on different parameters representing vital functions(i.e.,respiratory function,cardiovascular,and renal filtration parameters)at the moment of injury and 7 days post-injury in rats.No ventilatory parameters evaluated by plethys mography were impacted during quiet breathing after 7 days post-injury,whereas permanent diaphragm hemiplegia was observed by ultrasound and confirmed by diaphragmatic electromyography in anesthetized rats.Interestingly,the mean arterial pressure was reduced immediately after C2 hemisection,with complete compensation at 7 days post-injury.Renal filtration was unaffected at 7 days post-injury;however,remnant systolic dysfunction chara cterized by a reduced left ventricular ejection fraction persisted at 7 days post-injury.Taken together,these results demonstrated that following C2 hemisection,diaphragm activity and systolic function are impa cted up to 7 days post-injury,whereas the respiratory and cardiovascular systems display vast ada ptation to maintain ventilatory parameters and blood pressure homeostasis,with the latter likely sustained by the remaining descending sympathetic inputs spared by the initial injury.A better broad characterization of the physiopathology of high cervical spinal cord injuries covering a longer time period post-injury could be beneficial for understanding evaluations of putative therapeutics to further increase cardiorespiratory recovery.展开更多
Objective:With the increasing application of vascular reconstruction in surgical procedures,allogeneic vessels are becoming more popular in clinical practice due to their abundant sources,precise diameter matching,imp...Objective:With the increasing application of vascular reconstruction in surgical procedures,allogeneic vessels are becoming more popular in clinical practice due to their abundant sources,precise diameter matching,improved histocompatibility,and higher long-term patency rate.This study aimed to investigate the protective effect of various preservation solutions on the function and structure of the isolated rat abdominal aorta preserved under hypothermal conditions.Methods:The study utilized a total of 150 Sprague-Dawley(SD)rats,with 144 rats allocated to the experimental groups and 6 rats allocated to the control groups.The abdominal aorta of the rats was chosen as the subject of our research.The aorta in the experimental groups were randomly assigned to 4 groups:University of Wisconsin(UW)solution group,histidine-tryptophan-ketoglutarate(HTK)solution group,normal saline(NS)group,and sodium lactate Ringer's solution(RS)group.Samples were subjected to examination after preservation periods of 1 day,3 days,5 days,7 days,14 days,30 days,and 90 days.Evaluation of vascular physiological function involved detecting and assessing vasoconstriction ability and measuring cell viability through the MTT test.Evaluation of the vascular wall structure involved tension tolerance tests and pathological staining.Results:The pathogen-positive rate in the HTK group and NS group at 1 month was 16.7%.Regarding the vascular skeleton structure,both the UW group and HTK group exhibited intact structures after 2 weeks of preservation,with slightly edematous collagen and elastic fibers,which was significantly better than that of the NS group and RS group.In terms of cell activity and contractile function,all preservation groups showed similar effects within 2 weeks.However,after 2 weeks,the UW group showed the most favorable preservation effect(P<0.05).In terms of vascular tension,different groups exhibited similar effects within 1 week.However,after 2 weeks,the UW group showed the best preservation effect(P<0.05).Conclusion:All 4 types of preservation solution had a preservation effect on the structure and function of isolated blood vessels during short-term hypothermal preservation.However,after 2-week preservation,the UW solution was found to be the most suitable solution for the preservation of blood vessels.展开更多
Objective:To investigate the mechanism of action and material basis of AiTongXiao granule in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology and transplanted liver cancer rat model.Methods:...Objective:To investigate the mechanism of action and material basis of AiTongXiao granule in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology and transplanted liver cancer rat model.Methods:TCMSP database was used to screen out effective components and its corresponding potential pharmaceutical targets,and databases including Gene Cards,OMIM,Drugbank and TTD were further used to collect HCC-related drug targets.The intersecting targets were obtained by mapping the drug and disease targets.The component-targets network was constructed and visualized by Cytoscape 3.8.2 software.Protein-protein interaction(PPI)network was built by STRING online platform,and the topological relationship and core targets was analyzed and screened by using CytoNCA software.In addition,Metascape database was used to perform gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the core targets.At last,rat liver transplanted liver cancer model was established by using Walker-256 cell line and treated by AiTongXiao granule for 15 days.Western blot was used to further compare the expression levels of AKT,pAKT,p53,p-p53,ERK1/2 and ERK1/2 in the tumor between treatment group and the control group.Results:257 active components were obtained from AiTongXiao granule,corresponding to 294 drug targets.Meanwhile,233 of the 7993 HCC disease targets were screened out between AiTongXiao granule drug and HCC disease targets.11 core targets including AKT1,IL6,TP53,MAPK3,TNF,JUN,CASP3,MAPK1,MYC,PTGS2,MMP9 were further obtained by median screening.GO and KEGG analysis results showed that these core targets enriched to HBV,TNF and cancer related pathways.The rat transplanted liver cancer model results indicated significant down regulation for AKT,p-AKT,pERK1/2,and significant up regulation of p-p53 after AiTongXiao granule treatment(P<0.05).Conclusion:AiTongXiao granule could act to multiple cancer related pathways,and AKT,p53 and ERK1/2 were validated to be regulated by ATXF in rat model.The mechanism may be through the regulation of the above signaling pathways to exert anti-liver cancer effect.展开更多
Stress studies frequently utilize physical stressors to establish animal models of stress. In the majority of cases, these models are not consistent with human circumstances. The present study simulated a social isola...Stress studies frequently utilize physical stressors to establish animal models of stress. In the majority of cases, these models are not consistent with human circumstances. The present study simulated a social isolation plus resident intruder stress model in the rat. The rats were subjected to daily social isolation and resident intruder stress for 2 weeks. Behaviors were then tested. Rats subjected to social stress exhibited different aggressive behavior styles; some rats had greater scores on composite aggression behaviors, as well as locomotor and exploratory activity, but lower scores on latency than others. The high-aggressive group exhibited predominantly anger-out, while the low-aggressive group exhibited anger-in. Results suggest that social isolation plus resident intruder may serve as an appropriate model for anger-in and anger-out emotion modeling in the rat.展开更多
AIM:To investigate the efficacy of a Chinese medicine, Yi-gan-kang granule (granules for benefiting the liver), in prophylaxis and treatment of liver fibrosis in rats and its possible mechanism. METHODS: One hundred a...AIM:To investigate the efficacy of a Chinese medicine, Yi-gan-kang granule (granules for benefiting the liver), in prophylaxis and treatment of liver fibrosis in rats and its possible mechanism. METHODS: One hundred and forty Sprague-Dawley rats were randomly divided into seven groups (20 each): group 1, blank control group without any interference during the study; group 2, CCI4-induced liver fibrosis group; group 3, pig serum-induced liver fibrosis group; group 4, prophylaxis group of CCl4-induced liver fibrosis by Yi-gan-kang; group 5, prophylaxis group of pig serum-induced liver fibrosis by Yi-gan-kang; group 6, treatment group of CCI4-induced liver fibrosis by Yi-gan-kang; group 7, treatment group of CCI4-induced liver fibrosis by Yi-gan-kang. At wk 6,10,14 and 20 (baseline for CCl4., or big serum induction), five rats in each group were anesthetized and their livers were removed for pathological studies including immunohistochemical studies for α-SMA, type I collagen and In situ hybridization of tissue inhibitor of metalloproteinase-1 (TTMP-1) mRNA of hepatic stellate cells (HSCs). Anti-lipid peroxidation in isolated mitochondria and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) colorimetric assay for proliferation and terminal deoxynucleotidyl transferase-medicated dUTP-biotin nick end-labeling (TUNEL), flow cytometry and electron microscopy for apoptosis in isolated HSCs were also studied. RESULTS: The mean number of pseudolobuli at wk 10, 14 and 20 in the prophylaxis group was significantly less than that in the control group (P<0.05 or 0.01). The effect of prophylaxis at wk 14 in CCI4 rats and at wk 10 in pig serum-induced rats was much better than that of treatment group (P<0.01). The thickness (in μm) of fibers both in pig serum-induced prophylaxis and in treatment groups at wk 14 and. 20 was significantly less than that in control group (P<0.05). The number of fibers both in prophylaxis and in treatment groups from wk 10 or 14 to 20 was significantly less than that in control group (P<0.05 or P<0.01). The tissue HSC positive rates of type I collagen, α-SMA and TIMP-1 mRNA, which represented the active phenotype of HSCs in tissues, remained very high from wk 6 to the end of model making in control group. While in prophylaxis group, they were at a relatively low level. In treatment group, there was a gradual decreasing trend. Time- and dose-dependent effects of anti-lipid peroxidation on isolated mitochondria, cell proliferation and apoptosis in cultured HSCs were also observed during the study. CONCLUSION: Yi-gan-kang can effectively inhibit or inverse the course of liver fibrogenesis in CCI4- and pig serum-induced rat models.展开更多
AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following c...AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following conditions:(1)with different doses(20,10,5 mg/0.8 mL per rat);(2)with same dose in different concentrations(20 mg/rat,25,50 mg/mL);(3)in different ethanol percentage(25%,50%);and(4)at depth either 4 cm or 8 cm from anus.At 5 d and 4 wk after TNBS administration,inflammation severity and inflammation resolution were evaluated.At 4 and 8 wk after TNBS application,visceral hyperalgesia and enterochromaffin(EC)cell hyperplasia were assayed by abdominal withdrawal reflex test,silver staining and capillary electrophoresis. RESULTS:Our results showed that:(1)TNBS induced dose-dependent acute inflammation and inflammation resolution.At 5 d post TNBS,the pathological score and myeloperoxidase(MPO)activity in all TNBS treated rats were significantly elevated compared to that of the control(9.48±1.86,8.18±0.67,5.78± 0.77 vs 0,and 3.55±1.11,1.80±0.82,0.97±0.08 unit/mg vs 0.14±0.01 unit/mg,P<0.05).At 4 wk post TNBS,the pathological score in high and median dose TNBS-treated rats were still significantly higher than that of the control(1.52±0.38 and 0.80±0.35 vs 0,P<0.05);(2)Intracolonic TNBS administration position affected the persistence of visceral hyperalgesia.At 4 wk post TNBS,abdominal withdrawal reflex (AWR)threshold pressure in all TNBS-treated groups were decreased compared to that of the control(21.52 ±1.73 and 27.10±1.94 mmHg vs 34.44±1.89 mmHg,P<0.05).At 8 wk post TNBS,AWR threshold pressure in 8 cm administration group was still significantly decreased(23.33±1.33 mmHg vs 36.79±2.29 mmHg,P<0.05);(3)Ethanol percentage affected the TNBS-induced inflammation severity and visceral hyperalgesia.In TNBS-25%ethanol-treated group,the pathological score and MPO activity were significantly lowered compared to that of the TNBS-50%ethanoltreated group,while AWR threshold pressure were significantly elevated(36.33±0.61 mmHg vs 23.33±1.33 mmHg,P<0.05);and(4)TNBS(5 mg/0.8 mL per rat, in 50%ethanol,8 cm from anus)-treated rats recovered completely from the inflammation with acquired visceral hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration.CONCLUSION:TNBS dosage,concentration,intraco-lonic administration position,and ethanol percentage play important roles in developing visceral hyperalgesia and EC cell hyperplasia of TNBS-induced PI-IBS rats.展开更多
AIM:To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian Decoction(HYRD)on CCl4-induced hepatic fibrosis in rats and its modulation on the transforming growth factor(TGF)β-Smad signaling pathway.METHODS:Fif...AIM:To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian Decoction(HYRD)on CCl4-induced hepatic fibrosis in rats and its modulation on the transforming growth factor(TGF)β-Smad signaling pathway.METHODS:Fifty-six healthy Wistar rats were randomly divided into five groups:normal control group(n=6),CCl4-induced hepatic fibrosis group(n=14) and three treatment groups(the treated rats received HYRD via oral administration at daily dosages of 8.2,2.5 and 0.82 g/kg,respectively)of HYRD(n=12,respectively).Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution(CCl4 dissolved in peanut oil,4:6,V/V)with 0.5 mL/100 g body weight for the first time,and then 0.3 mL/100 g body weight twice a week for 8 wk.In the former 2 wk,rats were raised by feedstuffⅠ(80% corn meal,20%lard,0.5%cholesterol).After 2 wk,they were raised by feedstuffⅡ(corn meal and 0.5% cholesterol).Except for the control group,30%alcohol solution was given orally to each rat every other day from the beginning,1 mL for each rat.Liver function parameters and hepatic hydroxyproline content were detected by chromatometry.Serum levels of hyaluronic acid(HA),typeⅣcollagen(CIV),typeⅢprecollagen(PCⅢ)and laminin(LN)were assayed with radioimmunoassay.Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining.Gene expression of TGFβ1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting,respectively.RESULTS:The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group(P<0.01),and they were decreased in the three treatment groups compared with the model group.The serum levels of total protein and albumin were decreased in the model group and increased in the three treatment groups.The hepatic hydroxyproline content and serum levels of PCⅢ,HA,LN and CIV were markedly increased in the model group compared with the control group,and decreased in the treatment groups.The gene expression of TGFβ1 and Smad3 was enhanced in the model group compared with the control group,and HYRD could down regulate their expression.CONCLUSION:HYRD can inhibit hepatic fibrosis induced by CCl4 in rats,which is probably associated with its down-regulation on fibrogenic signal transduction of TGFβ-Smad pathway.展开更多
AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: control...AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site(1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1 AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC(Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB(0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01)(n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.展开更多
Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin i...Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin in a rat model of focal cerebral ischemia. Adult male Sprague-Dawley rat models of cerebral artery occlusion were established and then randomly and equally divided into three groups： ischemia（cerebral ischemia and reperfusion）, valproic acid（cerebral ischemia and reperfusion ＋ three intraperitoneal injections of valproic acid; positive control）, and baicalin（cerebral ischemia and reperfusion ＋ intraperitoneal injection of baicalin for 21 days）. Neurological deficits were assessed using the postural reflex test and forelimb placing test at 3, 7, 14, and 21 days after ischemia. Rat cerebral infarct volume was measured using 2,3,5-triphenyltetrazolium chloride（TTC） staining method. Pathological change of ischemic brain tissue was assessed using hematoxylin-eosin staining. In the baicalin group, rat neurological function was obviously improved, cerebral infarct volume was obviously reduced, and the pathological impairment of ischemic brain tissue was obviously alleviated compared to the ischemia group. Cerebral infarct volume was similar in the valproic acid and baicalin groups. These findings suggest that baicalin has a neuroprotective effect on cerebral ischemia.展开更多
AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal...AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal, high fat(HF), and HF containing 2-fluorenylacetamide(2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, pre-cancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-Ⅱ alterations were analyzed by immunohistochemistry, and compared with CPT-Ⅱ specific concentration(μg/mg protein). Levels of total cholesterol(Tch), triglyceride(TG), and aminotransferases [alanine aminotransferase(ALT), aspartate aminotransferase(AST)] were determined by the routine methods.RESULTS After intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls(P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher(4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-Ⅱ in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-Ⅱ levels in the cancer group than in any of the other groups(P < 0.05).CONCLUSION Low CPT-Ⅱ expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes.展开更多
AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in a...AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia.Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h,and 1,4,7,14,and 21d after irradiation.Tissue slices were evaluated histopathologically.Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count.Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups,blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour.The retinal detachment rate was 100%at 3h and developed into bullous retinal detachment within 24h.Retinal hemorrhages were not observed until 24h.Clearance of the occluded veins at 7d was observed by fluorescein angiography.Disease manifestation in the central RVO eyes was more severe than in the branch RVO group.A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d,whereas moderate changes occurred in the branch RVO group.CONCLUSION:Rat RVO created by photochemicallyinduced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO.However,considering the 100%rate ofretinal detachment,this animal model is more suitable for studying RVO with chronic retinal detachment.展开更多
AIM: To study the preventive effects of Qianggan-Rongxian Decoction on liver fibrosis induced by dimethylnitrosamine (DMN) in rats. METHODS: Male Wistar rats were randomly divided into hepatic fibrosis model group, co...AIM: To study the preventive effects of Qianggan-Rongxian Decoction on liver fibrosis induced by dimethylnitrosamine (DMN) in rats. METHODS: Male Wistar rats were randomly divided into hepatic fibrosis model group, control group and 3 treatment groups (12 rats in each group). Except for the normal control group, all the rats received 1% DMN (10 μL/kg body weight, i.p), 3 times a week for 4 wk. The rats in the 3 treatment groups including a high-dose DMN group (10 mL/kg), a medium-dose DMN group (7 mL/kg), and a low-dose DMN group (4 mL/kg) were daily gavaged with Qianggan-Rongxian Decoction, and the rats in the model and normal control groups were given saline vehicle. Enzyme-linked immunosorbent assay (ELISA) was used to determine the changes in serum hyaluronic acid (HA), laminin (LN), and type IV collagen levels. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using routine laboratory methods. Pathologic changes, particularly fibrosis, were examined by hematoxylin and eosin (HE) and Sirius red staining. Hepatic stellate cells (HSC) were examined by transmission electron microscopy. RESULTS: Compared with the model control group, the serum levels of HA, LN, type Ⅳ collagen, ALT and AST were decreased markedly in the other groups after treatment with Qianggan-Rongxian Decoction, especially in the medium-dose DMN group (P < 0.05).Moreover, the area-density percentage of collagen fibrosis was lower in the Qianggan-Rongxian Decoction treatment groups than in the model group, and a more significant drop was observed in the medium-dose DMN group (P < 0.05). CONCLUSION: Qianggan-Rongxian Decoction can inhibit hepatic fibrosis due to chronic liver injury, delay the development of cirrhosis, and notably ameliorate liver function. It may be used as a safe and effective thera-peutic drug for patients with fibrosis.展开更多
The use of autologous nerve grafts remains the gold standard for treating nerve defects, but current nerve repair techniques are limited by donor tissue availability and morbidity associated with tissue loss. Recently...The use of autologous nerve grafts remains the gold standard for treating nerve defects, but current nerve repair techniques are limited by donor tissue availability and morbidity associated with tissue loss. Recently, the use of conduits in nerve injury repair, made possible by tissue engineering, has shown therapeutic potential. We manufactured a biodegradable, collagen-based nerve conduit containing decellularized sciatic nerve matrix and compared this with a silicone conduit for peripheral nerve regeneration using a rat model. The collagen-based conduit contains nerve growth factor, brain-derived neurotrophic factor, and laminin, as demonstrated by enzyme-linked immunosorbent assay. Scanning electron microscopy images showed that the collagen-based conduit had an outer wall to prevent scar tissue infiltration and a porous inner structure to allow axonal growth. Rats that were implanted with the collagen-based conduit to bridge a sciatic nerve defect experienced significantly improved motor and sensory nerve functions and greatly enhanced nerve regeneration compared with rats in the sham control group and the silicone conduit group. Our results suggest that the biodegradable collagen-based nerve conduit is more effective for peripheral nerve regeneration than the silicone conduit.展开更多
The goal of this study was to increase the dopamine content and reduce dopaminergic metabolites in the brain of Parkinson’s disease rats. Using high-performance liquid chromatography, we found that dopamine and dopam...The goal of this study was to increase the dopamine content and reduce dopaminergic metabolites in the brain of Parkinson’s disease rats. Using high-performance liquid chromatography, we found that dopamine and dopaminergic metabolite（dihydroxyphenylacetic acid and homovanillic acid） content in the midbrain of Parkinson’s disease rats was increased after neural stem cell transplantation ＋ Zhichan decoction, compared with neural stem cell transplantation alone. Our genetic algorithm results show that dihydroxyphenylacetic acid and homovanillic acid levels achieve global optimization. Neural stem cell transplantation ＋ Zhichan decoction increased dihydroxyphenylacetic acid levels up to 10-fold, while transplantation alone resulted in a 3-fold increment. Homovanillic acid levels showed no apparent change. Our experimental findings show that after neural stem cell transplantation in Parkinson’s disease rats, Zhichan decoction can promote differentiation of neural stem cells into dopaminergic neurons.展开更多
BACKGROUND： Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he- patocellular carcinoma （HCC）. Pre-carcinoma and early HCC nodules are difficult to differentiate by observ...BACKGROUND： Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he- patocellular carcinoma （HCC）. Pre-carcinoma and early HCC nodules are difficult to differentiate by observing only their hemodynamics changes. The present study aimed to investi- gate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nodules using CT perfusion and receiver operating characteristic （ROC） curves. METHODS： Male Wistar rats were randomly divided into control （n=20） and experimental （n=70） groups. Diethylnitrosamine （DEN） was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion （HPP）, hepatic arterial fraction （HAF）, hepatic arterial perfusion （HAP）, hepatic blood volume （HBV）, hepatic blood flow （HBF）, mean transit time （MTT） and permeability of capillary vessel surface （PS） data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats （control, pre-carcinoma and early HCC groups） using the Kruskal-Wallis test and analyzed with ROC curves. Histological examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan.RESULTS： For HPP, HAF, HBV, HBF and MTT, there were significant differences among the three groups （P〈0.05）. HAF had the highest areas under the ROC curves： 0.80 （control vs pre-carcinoma groups） and 0.95 （control vs early HCC groups） with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 （control vs pre-carcinoma groups） and 0.92 （control vs early HCC groups） with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively. CONCLUSIONS： CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.展开更多
Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury ...Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.展开更多
AIM： To study the inhibitory effect of mononuclear bone marrow cell （BNC） transplantation on carbon tetrachloride （CCl4） -induced liver fibrosis in rats. METHODS： Rat liver fibrosis models were induced by CCl4 a...AIM： To study the inhibitory effect of mononuclear bone marrow cell （BNC） transplantation on carbon tetrachloride （CCl4） -induced liver fibrosis in rats. METHODS： Rat liver fibrosis models were induced by CCl4 and alcohol administration. After 8 wk, twenty rats were randomly allocated into treatment group （n = 10） and control group （n = 10）. BMC were infused into the rats in treatment group via the portal vein, while heparinized saline was infused in control group. CCl4 was hypodermically injected into the rats twice a week for 4 wk. At the end of wk 12, all rats were humanely sacrificed. Uver samples were taken and stained with HE or Masson trichrome. The general conditions, liver fibrosis （hydroxyproline and collagen fibre） and liver pathological grades in rats were evaluated. RESULTS： The general conditions of the rats in treatment group improved markedly, but not in control group. Hydroxyproline was 504.6± 128.8 μg/g in treatment group, and 596.0 ± 341.8 μg/g in control group. The percentage of collagen fibre was 3.75% ± 0.98% in treatment group and 5.02% ± 0.44% in control group. There was a significant difference between the two groups （P 〈 0.05）. Liver pathological grade decreased from grade N to grade 11 partially in treatment group （P 〈 0.05） with no obvious improvement in control group （P 〉 0.05）. There was a significant difference between treatment group and control group （P 〈 0.05）.CONCLUSION： Transplantation of BMC can improve liver fibrosis due to chronic liver injury in rats.展开更多
AIM： To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS： Ocular hypertension was induced in right eyes of Long-Evans rats （n=30） by cauterization of three episcle...AIM： To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS： Ocular hypertension was induced in right eyes of Long-Evans rats （n=30） by cauterization of three episcleral veins. Left eyes were defined as controls. Rats were divided into five groups： oral rosuvastatin, intravitreal rosuvastatin, oral ＋intravitreal rosuvastatin, intravitreal sham and glaucoma without intervention. Rats were sacrificed at day 14. Retinal ganglion cell （RGC） number was assessed by histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling （TUNEL） staining and the expression of glial fibrillary acidic protein （GFAP） in RGC layer was also examined. RESULTS： A significant intraocular pressure （lOP） elevation was seen （P=0.002）. Elevated lOP resulted in a significant decrease in number of RGCs in group 5 （70.33 ±8.2 cells/mm2） when compared with controls （92.50 ±13.72 cells/mm2; P=0.03）. The RGC number in group 1 （92.4±7.3 cells/mm2） was significantly higher than group 5 （ρ=0.03）. The numbers of RGC in groups 2, 3 （57.3±8.2 cells/mm2, 60.5±12.9 cells/mm2） were comparable with that of group 5 （ρ=0.18 and P=0.31）. The apoptosis rates with TUNEL staining were also parallel to RGC number. Animals with experimentally induced glaucoma showed an increase in retinal GFAP immunoreacUvity. CONCLUSION： Decrease in RGC loss and apoptosis suggest the neuroprotective potential of oral rosuvastatin treatment in a rat model of ocular hypertension. Howeverintravitreal rosuvastatin showed a contrary effect and further studies are required.展开更多
基金supported by grants The Natural Science Foundation of Inner Mongolia(2019MS08104)The Natural Science Foundation of Inner Mongolia(2022ZD09)The Central Government Guiding Special Funds for Development of Local Science and Technology(2020ZY0020).
文摘Background:The active components of Horcha-6 were identified using liquid chromatography with tandem mass spectrometry.Also,we investigated the potential mechanisms that explain why Horcha-6 may be effective in treating migraines through the use of network pharmacology and a rat migraine model.Methods:After identifying the active components of Horcha-6,the corresponding genes of the active components’target were obtained from the Universal Protein database,and a“compound-target-disease”network was constructed using Cytoscape 3.9.0 software.For the in vivo experiments,nitroglycerin was injected intraperitoneally into rats to create a migraine model.Pre-treatment with Horcha-6 was administered orally for 14 days,and rats were subjected to migraine-related behavior tests.RNA sequencing was performed to identify the gene expression regulated by Horcha-6 in the trigeminal nerve.Results:A total of 903 chemical components of Horcha-6 have been collected in the liquid chromatography with tandem mass spectrometry.We discovered 55 of the Horcha-6 bio-active components that were evaluated based on their Percent Human Oral Absorption(≥30%)and DL values(≥0.185)on the traditional Chinese medicine systems pharmacology database.The“compound-target-disease”network contained 163 intersection targets with the migraine state.Gene Ontology analysis indicated that these components significantly regulated the immune response,vascular function,oxidative stress,etc.When Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed,we observed that most of the target genes were significantly enriched in the inflammation and neuro-related signaling pathway,toll-like receptor signaling pathway,neuroactive ligand-receptor interaction,etc.These predictions were further demonstrated via in vivo animal model experiments.The RNA sequencing results showed that 41 genes were down-regulated(P<0.05)and 86 genes were up-regulated(P<0.05)in the Horcha-6 treated group compared with the untreated group.Those genes were mainly involved in neuromodulation,vascular function,and hormone metabolism.Conclusion:The 55 bio-active components in Horcha-6 regulate inflammation,hormone metabolism,and neurotransmitters and have potential as a therapy to treat migraines.
基金Foundation items： The preparation of this review was partially supported by a grant from the National Institute of Mental Health （5R01 MH097718-02）, U.S.A.
文摘The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions.
基金supported by funding from the Chancellerie des Universites de Paris(Legs Poix)(to SV)Fondation Medisite(to SV)+1 种基金INSERM(to SV,AM,AF)Universite de Versailles Saint-Quentin-en-Yvelines(to SV,AM,AF)。
文摘High ce rvical spinal co rd injuries induce permanent neuromotor and autonomic deficits.These injuries impact both central respiratory and cardiovascular functions through modulation of the sympathetic nervous system.So far,cardiovascular studies have focused on models of complete contusion or transection at the lower cervical and thoracic levels and diaphragm activity evaluations using invasive methods.The present study aimed to evaluate the impact of C2 hemisection on different parameters representing vital functions(i.e.,respiratory function,cardiovascular,and renal filtration parameters)at the moment of injury and 7 days post-injury in rats.No ventilatory parameters evaluated by plethys mography were impacted during quiet breathing after 7 days post-injury,whereas permanent diaphragm hemiplegia was observed by ultrasound and confirmed by diaphragmatic electromyography in anesthetized rats.Interestingly,the mean arterial pressure was reduced immediately after C2 hemisection,with complete compensation at 7 days post-injury.Renal filtration was unaffected at 7 days post-injury;however,remnant systolic dysfunction chara cterized by a reduced left ventricular ejection fraction persisted at 7 days post-injury.Taken together,these results demonstrated that following C2 hemisection,diaphragm activity and systolic function are impa cted up to 7 days post-injury,whereas the respiratory and cardiovascular systems display vast ada ptation to maintain ventilatory parameters and blood pressure homeostasis,with the latter likely sustained by the remaining descending sympathetic inputs spared by the initial injury.A better broad characterization of the physiopathology of high cervical spinal cord injuries covering a longer time period post-injury could be beneficial for understanding evaluations of putative therapeutics to further increase cardiorespiratory recovery.
文摘Objective:With the increasing application of vascular reconstruction in surgical procedures,allogeneic vessels are becoming more popular in clinical practice due to their abundant sources,precise diameter matching,improved histocompatibility,and higher long-term patency rate.This study aimed to investigate the protective effect of various preservation solutions on the function and structure of the isolated rat abdominal aorta preserved under hypothermal conditions.Methods:The study utilized a total of 150 Sprague-Dawley(SD)rats,with 144 rats allocated to the experimental groups and 6 rats allocated to the control groups.The abdominal aorta of the rats was chosen as the subject of our research.The aorta in the experimental groups were randomly assigned to 4 groups:University of Wisconsin(UW)solution group,histidine-tryptophan-ketoglutarate(HTK)solution group,normal saline(NS)group,and sodium lactate Ringer's solution(RS)group.Samples were subjected to examination after preservation periods of 1 day,3 days,5 days,7 days,14 days,30 days,and 90 days.Evaluation of vascular physiological function involved detecting and assessing vasoconstriction ability and measuring cell viability through the MTT test.Evaluation of the vascular wall structure involved tension tolerance tests and pathological staining.Results:The pathogen-positive rate in the HTK group and NS group at 1 month was 16.7%.Regarding the vascular skeleton structure,both the UW group and HTK group exhibited intact structures after 2 weeks of preservation,with slightly edematous collagen and elastic fibers,which was significantly better than that of the NS group and RS group.In terms of cell activity and contractile function,all preservation groups showed similar effects within 2 weeks.However,after 2 weeks,the UW group showed the most favorable preservation effect(P<0.05).In terms of vascular tension,different groups exhibited similar effects within 1 week.However,after 2 weeks,the UW group showed the best preservation effect(P<0.05).Conclusion:All 4 types of preservation solution had a preservation effect on the structure and function of isolated blood vessels during short-term hypothermal preservation.However,after 2-week preservation,the UW solution was found to be the most suitable solution for the preservation of blood vessels.
基金Guangxi Science and Technology Base and Talent Project (Guike AD20297013)Guangxi Natural Science Foundat ion Project (2021GXNSFBA220036)The second batch of"Qihuang Project"High-Level Talent Team Cultivation Project of Guangxi University of Traditional Chinese Medicine (2021001)。
文摘Objective:To investigate the mechanism of action and material basis of AiTongXiao granule in the treatment of hepatocellular carcinoma(HCC)based on network pharmacology and transplanted liver cancer rat model.Methods:TCMSP database was used to screen out effective components and its corresponding potential pharmaceutical targets,and databases including Gene Cards,OMIM,Drugbank and TTD were further used to collect HCC-related drug targets.The intersecting targets were obtained by mapping the drug and disease targets.The component-targets network was constructed and visualized by Cytoscape 3.8.2 software.Protein-protein interaction(PPI)network was built by STRING online platform,and the topological relationship and core targets was analyzed and screened by using CytoNCA software.In addition,Metascape database was used to perform gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis of the core targets.At last,rat liver transplanted liver cancer model was established by using Walker-256 cell line and treated by AiTongXiao granule for 15 days.Western blot was used to further compare the expression levels of AKT,pAKT,p53,p-p53,ERK1/2 and ERK1/2 in the tumor between treatment group and the control group.Results:257 active components were obtained from AiTongXiao granule,corresponding to 294 drug targets.Meanwhile,233 of the 7993 HCC disease targets were screened out between AiTongXiao granule drug and HCC disease targets.11 core targets including AKT1,IL6,TP53,MAPK3,TNF,JUN,CASP3,MAPK1,MYC,PTGS2,MMP9 were further obtained by median screening.GO and KEGG analysis results showed that these core targets enriched to HBV,TNF and cancer related pathways.The rat transplanted liver cancer model results indicated significant down regulation for AKT,p-AKT,pERK1/2,and significant up regulation of p-p53 after AiTongXiao granule treatment(P<0.05).Conclusion:AiTongXiao granule could act to multiple cancer related pathways,and AKT,p53 and ERK1/2 were validated to be regulated by ATXF in rat model.The mechanism may be through the regulation of the above signaling pathways to exert anti-liver cancer effect.
基金the National Natural Science Foundation of China,No.30973688the National Program of Key Basic Research Project(973Program),No.2006CB504804
文摘Stress studies frequently utilize physical stressors to establish animal models of stress. In the majority of cases, these models are not consistent with human circumstances. The present study simulated a social isolation plus resident intruder stress model in the rat. The rats were subjected to daily social isolation and resident intruder stress for 2 weeks. Behaviors were then tested. Rats subjected to social stress exhibited different aggressive behavior styles; some rats had greater scores on composite aggression behaviors, as well as locomotor and exploratory activity, but lower scores on latency than others. The high-aggressive group exhibited predominantly anger-out, while the low-aggressive group exhibited anger-in. Results suggest that social isolation plus resident intruder may serve as an appropriate model for anger-in and anger-out emotion modeling in the rat.
基金Supported by the Natural Science Foundation of Hebei Province,No. 300358
文摘AIM:To investigate the efficacy of a Chinese medicine, Yi-gan-kang granule (granules for benefiting the liver), in prophylaxis and treatment of liver fibrosis in rats and its possible mechanism. METHODS: One hundred and forty Sprague-Dawley rats were randomly divided into seven groups (20 each): group 1, blank control group without any interference during the study; group 2, CCI4-induced liver fibrosis group; group 3, pig serum-induced liver fibrosis group; group 4, prophylaxis group of CCl4-induced liver fibrosis by Yi-gan-kang; group 5, prophylaxis group of pig serum-induced liver fibrosis by Yi-gan-kang; group 6, treatment group of CCI4-induced liver fibrosis by Yi-gan-kang; group 7, treatment group of CCI4-induced liver fibrosis by Yi-gan-kang. At wk 6,10,14 and 20 (baseline for CCl4., or big serum induction), five rats in each group were anesthetized and their livers were removed for pathological studies including immunohistochemical studies for α-SMA, type I collagen and In situ hybridization of tissue inhibitor of metalloproteinase-1 (TTMP-1) mRNA of hepatic stellate cells (HSCs). Anti-lipid peroxidation in isolated mitochondria and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) colorimetric assay for proliferation and terminal deoxynucleotidyl transferase-medicated dUTP-biotin nick end-labeling (TUNEL), flow cytometry and electron microscopy for apoptosis in isolated HSCs were also studied. RESULTS: The mean number of pseudolobuli at wk 10, 14 and 20 in the prophylaxis group was significantly less than that in the control group (P<0.05 or 0.01). The effect of prophylaxis at wk 14 in CCI4 rats and at wk 10 in pig serum-induced rats was much better than that of treatment group (P<0.01). The thickness (in μm) of fibers both in pig serum-induced prophylaxis and in treatment groups at wk 14 and. 20 was significantly less than that in control group (P<0.05). The number of fibers both in prophylaxis and in treatment groups from wk 10 or 14 to 20 was significantly less than that in control group (P<0.05 or P<0.01). The tissue HSC positive rates of type I collagen, α-SMA and TIMP-1 mRNA, which represented the active phenotype of HSCs in tissues, remained very high from wk 6 to the end of model making in control group. While in prophylaxis group, they were at a relatively low level. In treatment group, there was a gradual decreasing trend. Time- and dose-dependent effects of anti-lipid peroxidation on isolated mitochondria, cell proliferation and apoptosis in cultured HSCs were also observed during the study. CONCLUSION: Yi-gan-kang can effectively inhibit or inverse the course of liver fibrogenesis in CCI4- and pig serum-induced rat models.
基金Supported by Hong Kong Jockey Club Institute of Chinese Medicine,No.JCICM-4-07
文摘AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following conditions:(1)with different doses(20,10,5 mg/0.8 mL per rat);(2)with same dose in different concentrations(20 mg/rat,25,50 mg/mL);(3)in different ethanol percentage(25%,50%);and(4)at depth either 4 cm or 8 cm from anus.At 5 d and 4 wk after TNBS administration,inflammation severity and inflammation resolution were evaluated.At 4 and 8 wk after TNBS application,visceral hyperalgesia and enterochromaffin(EC)cell hyperplasia were assayed by abdominal withdrawal reflex test,silver staining and capillary electrophoresis. RESULTS:Our results showed that:(1)TNBS induced dose-dependent acute inflammation and inflammation resolution.At 5 d post TNBS,the pathological score and myeloperoxidase(MPO)activity in all TNBS treated rats were significantly elevated compared to that of the control(9.48±1.86,8.18±0.67,5.78± 0.77 vs 0,and 3.55±1.11,1.80±0.82,0.97±0.08 unit/mg vs 0.14±0.01 unit/mg,P<0.05).At 4 wk post TNBS,the pathological score in high and median dose TNBS-treated rats were still significantly higher than that of the control(1.52±0.38 and 0.80±0.35 vs 0,P<0.05);(2)Intracolonic TNBS administration position affected the persistence of visceral hyperalgesia.At 4 wk post TNBS,abdominal withdrawal reflex (AWR)threshold pressure in all TNBS-treated groups were decreased compared to that of the control(21.52 ±1.73 and 27.10±1.94 mmHg vs 34.44±1.89 mmHg,P<0.05).At 8 wk post TNBS,AWR threshold pressure in 8 cm administration group was still significantly decreased(23.33±1.33 mmHg vs 36.79±2.29 mmHg,P<0.05);(3)Ethanol percentage affected the TNBS-induced inflammation severity and visceral hyperalgesia.In TNBS-25%ethanol-treated group,the pathological score and MPO activity were significantly lowered compared to that of the TNBS-50%ethanoltreated group,while AWR threshold pressure were significantly elevated(36.33±0.61 mmHg vs 23.33±1.33 mmHg,P<0.05);and(4)TNBS(5 mg/0.8 mL per rat, in 50%ethanol,8 cm from anus)-treated rats recovered completely from the inflammation with acquired visceral hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration.CONCLUSION:TNBS dosage,concentration,intraco-lonic administration position,and ethanol percentage play important roles in developing visceral hyperalgesia and EC cell hyperplasia of TNBS-induced PI-IBS rats.
基金Supported by The Major Project of Applied Basic Research Plan of the Scientific and Technological Department of Tianjin,No.06YFJZJC02900
文摘AIM:To explore the anti-fibrotic effect of Haobie Yangyin Ruanjian Decoction(HYRD)on CCl4-induced hepatic fibrosis in rats and its modulation on the transforming growth factor(TGF)β-Smad signaling pathway.METHODS:Fifty-six healthy Wistar rats were randomly divided into five groups:normal control group(n=6),CCl4-induced hepatic fibrosis group(n=14) and three treatment groups(the treated rats received HYRD via oral administration at daily dosages of 8.2,2.5 and 0.82 g/kg,respectively)of HYRD(n=12,respectively).Experimental hepatic fibrosis was induced by subcutaneous injection of carbon tetrachloride solution(CCl4 dissolved in peanut oil,4:6,V/V)with 0.5 mL/100 g body weight for the first time,and then 0.3 mL/100 g body weight twice a week for 8 wk.In the former 2 wk,rats were raised by feedstuffⅠ(80% corn meal,20%lard,0.5%cholesterol).After 2 wk,they were raised by feedstuffⅡ(corn meal and 0.5% cholesterol).Except for the control group,30%alcohol solution was given orally to each rat every other day from the beginning,1 mL for each rat.Liver function parameters and hepatic hydroxyproline content were detected by chromatometry.Serum levels of hyaluronic acid(HA),typeⅣcollagen(CIV),typeⅢprecollagen(PCⅢ)and laminin(LN)were assayed with radioimmunoassay.Deposition of collagen was observed with hematoxylin-eosin staining and collagen staining.Gene expression of TGFβ1 and Smad3 were detected with real-time reverse transcriptase-polymerase chain reaction and Western blotting,respectively.RESULTS:The serum levels of alanine transaminase and aspartate transaminase were increased in the model group compared with the control group(P<0.01),and they were decreased in the three treatment groups compared with the model group.The serum levels of total protein and albumin were decreased in the model group and increased in the three treatment groups.The hepatic hydroxyproline content and serum levels of PCⅢ,HA,LN and CIV were markedly increased in the model group compared with the control group,and decreased in the treatment groups.The gene expression of TGFβ1 and Smad3 was enhanced in the model group compared with the control group,and HYRD could down regulate their expression.CONCLUSION:HYRD can inhibit hepatic fibrosis induced by CCl4 in rats,which is probably associated with its down-regulation on fibrogenic signal transduction of TGFβ-Smad pathway.
文摘AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site(1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1 AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC(Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB(0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01)(n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.
基金supported by the Cross Foundation Major Project of Engineering and Medicine of Shanghai Jiao Tong University,No.YG2016MS50(to JD)Foundation for Fostering Project of Clinical Study on Multi-disciplinary Team of Renji Hospital,No.PYMDT-012(to JD)
文摘Baicalin, a flavonoid compound from the root of the herb Scutellaria baicalensis Georgi, has been widely used to treat patients with inflammatory disease. The aim of this study was to assess the efficacy of baicalin in a rat model of focal cerebral ischemia. Adult male Sprague-Dawley rat models of cerebral artery occlusion were established and then randomly and equally divided into three groups： ischemia（cerebral ischemia and reperfusion）, valproic acid（cerebral ischemia and reperfusion ＋ three intraperitoneal injections of valproic acid; positive control）, and baicalin（cerebral ischemia and reperfusion ＋ intraperitoneal injection of baicalin for 21 days）. Neurological deficits were assessed using the postural reflex test and forelimb placing test at 3, 7, 14, and 21 days after ischemia. Rat cerebral infarct volume was measured using 2,3,5-triphenyltetrazolium chloride（TTC） staining method. Pathological change of ischemic brain tissue was assessed using hematoxylin-eosin staining. In the baicalin group, rat neurological function was obviously improved, cerebral infarct volume was obviously reduced, and the pathological impairment of ischemic brain tissue was obviously alleviated compared to the ischemia group. Cerebral infarct volume was similar in the valproic acid and baicalin groups. These findings suggest that baicalin has a neuroprotective effect on cerebral ischemia.
基金Supported by the National Natural Science Foundation,No.81673241,No.81200634,No.81370982the program of Jiangsu Key Research Plan,No.BE2016698the International Science and Technology Cooperation Program of China,No.2013DFA32150
文摘AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal, high fat(HF), and HF containing 2-fluorenylacetamide(2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, pre-cancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-Ⅱ alterations were analyzed by immunohistochemistry, and compared with CPT-Ⅱ specific concentration(μg/mg protein). Levels of total cholesterol(Tch), triglyceride(TG), and aminotransferases [alanine aminotransferase(ALT), aspartate aminotransferase(AST)] were determined by the routine methods.RESULTS After intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls(P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher(4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-Ⅱ in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-Ⅱ levels in the cancer group than in any of the other groups(P < 0.05).CONCLUSION Low CPT-Ⅱ expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes.
基金Supported by National Natural Science Foundation of China(No.81100681)
文摘AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia.Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h,and 1,4,7,14,and 21d after irradiation.Tissue slices were evaluated histopathologically.Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count.Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups,blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour.The retinal detachment rate was 100%at 3h and developed into bullous retinal detachment within 24h.Retinal hemorrhages were not observed until 24h.Clearance of the occluded veins at 7d was observed by fluorescein angiography.Disease manifestation in the central RVO eyes was more severe than in the branch RVO group.A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d,whereas moderate changes occurred in the branch RVO group.CONCLUSION:Rat RVO created by photochemicallyinduced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO.However,considering the 100%rate ofretinal detachment,this animal model is more suitable for studying RVO with chronic retinal detachment.
基金the Research Program of Department of Scienceand Technology of Hebei Province, No. 200721047
文摘AIM: To study the preventive effects of Qianggan-Rongxian Decoction on liver fibrosis induced by dimethylnitrosamine (DMN) in rats. METHODS: Male Wistar rats were randomly divided into hepatic fibrosis model group, control group and 3 treatment groups (12 rats in each group). Except for the normal control group, all the rats received 1% DMN (10 μL/kg body weight, i.p), 3 times a week for 4 wk. The rats in the 3 treatment groups including a high-dose DMN group (10 mL/kg), a medium-dose DMN group (7 mL/kg), and a low-dose DMN group (4 mL/kg) were daily gavaged with Qianggan-Rongxian Decoction, and the rats in the model and normal control groups were given saline vehicle. Enzyme-linked immunosorbent assay (ELISA) was used to determine the changes in serum hyaluronic acid (HA), laminin (LN), and type IV collagen levels. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured using routine laboratory methods. Pathologic changes, particularly fibrosis, were examined by hematoxylin and eosin (HE) and Sirius red staining. Hepatic stellate cells (HSC) were examined by transmission electron microscopy. RESULTS: Compared with the model control group, the serum levels of HA, LN, type Ⅳ collagen, ALT and AST were decreased markedly in the other groups after treatment with Qianggan-Rongxian Decoction, especially in the medium-dose DMN group (P < 0.05).Moreover, the area-density percentage of collagen fibrosis was lower in the Qianggan-Rongxian Decoction treatment groups than in the model group, and a more significant drop was observed in the medium-dose DMN group (P < 0.05). CONCLUSION: Qianggan-Rongxian Decoction can inhibit hepatic fibrosis due to chronic liver injury, delay the development of cirrhosis, and notably ameliorate liver function. It may be used as a safe and effective thera-peutic drug for patients with fibrosis.
基金supported by a grant from the Small and Medium Business Administration(S2082152)
文摘The use of autologous nerve grafts remains the gold standard for treating nerve defects, but current nerve repair techniques are limited by donor tissue availability and morbidity associated with tissue loss. Recently, the use of conduits in nerve injury repair, made possible by tissue engineering, has shown therapeutic potential. We manufactured a biodegradable, collagen-based nerve conduit containing decellularized sciatic nerve matrix and compared this with a silicone conduit for peripheral nerve regeneration using a rat model. The collagen-based conduit contains nerve growth factor, brain-derived neurotrophic factor, and laminin, as demonstrated by enzyme-linked immunosorbent assay. Scanning electron microscopy images showed that the collagen-based conduit had an outer wall to prevent scar tissue infiltration and a porous inner structure to allow axonal growth. Rats that were implanted with the collagen-based conduit to bridge a sciatic nerve defect experienced significantly improved motor and sensory nerve functions and greatly enhanced nerve regeneration compared with rats in the sham control group and the silicone conduit group. Our results suggest that the biodegradable collagen-based nerve conduit is more effective for peripheral nerve regeneration than the silicone conduit.
基金financially supported by the National Natural Science Foundation of China,No.30772870
文摘The goal of this study was to increase the dopamine content and reduce dopaminergic metabolites in the brain of Parkinson’s disease rats. Using high-performance liquid chromatography, we found that dopamine and dopaminergic metabolite（dihydroxyphenylacetic acid and homovanillic acid） content in the midbrain of Parkinson’s disease rats was increased after neural stem cell transplantation ＋ Zhichan decoction, compared with neural stem cell transplantation alone. Our genetic algorithm results show that dihydroxyphenylacetic acid and homovanillic acid levels achieve global optimization. Neural stem cell transplantation ＋ Zhichan decoction increased dihydroxyphenylacetic acid levels up to 10-fold, while transplantation alone resulted in a 3-fold increment. Homovanillic acid levels showed no apparent change. Our experimental findings show that after neural stem cell transplantation in Parkinson’s disease rats, Zhichan decoction can promote differentiation of neural stem cells into dopaminergic neurons.
基金supported by grants from the National Natural Science Foundation of China(81301275,81471736 and 81671760)the National Science and Technology Pillar Program during the Twelfth Five-Year Plan Period(2015BAI01B09)Heilongjiang Province Foundation for Returness(LC2013C38)
文摘BACKGROUND： Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he- patocellular carcinoma （HCC）. Pre-carcinoma and early HCC nodules are difficult to differentiate by observing only their hemodynamics changes. The present study aimed to investi- gate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nodules using CT perfusion and receiver operating characteristic （ROC） curves. METHODS： Male Wistar rats were randomly divided into control （n=20） and experimental （n=70） groups. Diethylnitrosamine （DEN） was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion （HPP）, hepatic arterial fraction （HAF）, hepatic arterial perfusion （HAP）, hepatic blood volume （HBV）, hepatic blood flow （HBF）, mean transit time （MTT） and permeability of capillary vessel surface （PS） data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats （control, pre-carcinoma and early HCC groups） using the Kruskal-Wallis test and analyzed with ROC curves. Histological examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan.RESULTS： For HPP, HAF, HBV, HBF and MTT, there were significant differences among the three groups （P〈0.05）. HAF had the highest areas under the ROC curves： 0.80 （control vs pre-carcinoma groups） and 0.95 （control vs early HCC groups） with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 （control vs pre-carcinoma groups） and 0.92 （control vs early HCC groups） with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively. CONCLUSIONS： CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.
基金Supported by the National Natural Science Foundation of China(Nos.30700884,30873145)the Distinguished Middle-aged and Young Scientist Encourage and Reward Foundation of Shandong Province,China(No.BS2009SW015)
文摘Cardiac ischemia/reperfusion（I/R） injury is a critical condition,often associated with high morbidity and mortality.The cardioprotective effect of grape seed proanthocyanidin extracts（GSPE） against oxidant injury during I/R has been described in previous studies.However,the underlying molecular mechanisms have not been fully elucidated.This study investigated the effect of GSPE on reperfusion arrhythmias especially ventricular tachycardia（VT） and ventricular fibrillation（VF）,the lactic acid accumulation and the ultrastructure of ischemic cardiomyocytes as well as the global changes of mitochondria proteins in in vivo rat heart model against I/R injury.GSPE significantly reduced the incidence of VF and VT,lessened the lactic acid accumulation and attenuated the ultrastructure damage.Twenty differential proteins related to cardiac protection were revealed by isobaric tag for relative and absolute quantitation（iTRAQ） profiling.These proteins were mainly involved in energy metabolism.Besides,monoamine oxidase A（MAOA） was also identified.The differential expression of several proteins was validated by Western blot.Our study offered important information on the mechanism of GSPE treatment in ischemic heart disease.
基金the Key Scientific and Technological Projects of Guangdong Province, No. 2005A30201007Guangdong Provincial Natural Science Fundation, No. 06021343
文摘AIM： To study the inhibitory effect of mononuclear bone marrow cell （BNC） transplantation on carbon tetrachloride （CCl4） -induced liver fibrosis in rats. METHODS： Rat liver fibrosis models were induced by CCl4 and alcohol administration. After 8 wk, twenty rats were randomly allocated into treatment group （n = 10） and control group （n = 10）. BMC were infused into the rats in treatment group via the portal vein, while heparinized saline was infused in control group. CCl4 was hypodermically injected into the rats twice a week for 4 wk. At the end of wk 12, all rats were humanely sacrificed. Uver samples were taken and stained with HE or Masson trichrome. The general conditions, liver fibrosis （hydroxyproline and collagen fibre） and liver pathological grades in rats were evaluated. RESULTS： The general conditions of the rats in treatment group improved markedly, but not in control group. Hydroxyproline was 504.6± 128.8 μg/g in treatment group, and 596.0 ± 341.8 μg/g in control group. The percentage of collagen fibre was 3.75% ± 0.98% in treatment group and 5.02% ± 0.44% in control group. There was a significant difference between the two groups （P 〈 0.05）. Liver pathological grade decreased from grade N to grade 11 partially in treatment group （P 〈 0.05） with no obvious improvement in control group （P 〉 0.05）. There was a significant difference between treatment group and control group （P 〈 0.05）.CONCLUSION： Transplantation of BMC can improve liver fibrosis due to chronic liver injury in rats.
基金Supported by Gazi University Research and Education Fund
文摘AIM： To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS： Ocular hypertension was induced in right eyes of Long-Evans rats （n=30） by cauterization of three episcleral veins. Left eyes were defined as controls. Rats were divided into five groups： oral rosuvastatin, intravitreal rosuvastatin, oral ＋intravitreal rosuvastatin, intravitreal sham and glaucoma without intervention. Rats were sacrificed at day 14. Retinal ganglion cell （RGC） number was assessed by histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling （TUNEL） staining and the expression of glial fibrillary acidic protein （GFAP） in RGC layer was also examined. RESULTS： A significant intraocular pressure （lOP） elevation was seen （P=0.002）. Elevated lOP resulted in a significant decrease in number of RGCs in group 5 （70.33 ±8.2 cells/mm2） when compared with controls （92.50 ±13.72 cells/mm2; P=0.03）. The RGC number in group 1 （92.4±7.3 cells/mm2） was significantly higher than group 5 （ρ=0.03）. The numbers of RGC in groups 2, 3 （57.3±8.2 cells/mm2, 60.5±12.9 cells/mm2） were comparable with that of group 5 （ρ=0.18 and P=0.31）. The apoptosis rates with TUNEL staining were also parallel to RGC number. Animals with experimentally induced glaucoma showed an increase in retinal GFAP immunoreacUvity. CONCLUSION： Decrease in RGC loss and apoptosis suggest the neuroprotective potential of oral rosuvastatin treatment in a rat model of ocular hypertension. Howeverintravitreal rosuvastatin showed a contrary effect and further studies are required.
