Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse model.Methods:We created a mouse model of dep...Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse model.Methods:We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections.The mice were divided into the following groups:control,model,fluoxetine,Tiansi Yin,Sini powder,and low-,medium-,and high-dose Peiyuan Jieyu formula groups.Forced swim and tail suspension tests were used to assess the efficacy of the depression(despair)model,and weight gain rates were also measured.Furthermore,serum levels of various depression and inflammation-associated molecules,including tumor necrosis factor-a(TNF-a),interferon-γ(IFN-γ),tryptophan,5-hydroxytryptamine,kynurenine(KYN),and kynurenic acid(KA)were assessed.Furthermore,the expression levels of ionic calcium-binding adaptor molecule-1(IBA-1)and indoleamine 2,3-dioxygenase(IDO)mRNA in hippocampal microglia were measured.Results:The model group displayed greater despair-associated immobility,which was shortened in response to various doses of Peiyuan Jieyu formula.Furthermore,formula administration significantly reduced serum TNF-a levels and hippocampal IDO mRNA expression.The high formula dose also reduced IFN-γand IBA-1 levels,the latter was also decreased in response to the medium formula dose.However,the low formula dose reduced serum KYN level and KYN/tryptophan(TRP)and KYN/KA ratios.Conclusion:The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model,potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.展开更多
Objective:To study the effects of social stress(CS)and social stress combined with high-fat diet on fat mobilization as a candidate mechanism for the induction or aggravation of non-alcoholic fatty liver disease(NAFLD...Objective:To study the effects of social stress(CS)and social stress combined with high-fat diet on fat mobilization as a candidate mechanism for the induction or aggravation of non-alcoholic fatty liver disease(NAFLD).Methods:Thirty-two male Wistar rats(250±10 g)were randomly allocated to a blank control group(BC),a high-fat diet group(HFD),a CS group,and a combined CS and high-fat diet group(CS t HFD).Rats were sacrificed and tissues were collected after 8 weeks.Liver and body mass were measured and used to calculate the liver index.Serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),and free fatty acids(FFAs)were measured.Liver sections were examined microscopically after oil red O and hematoxylin and eosin staining.The relative mRNA expression of acetyl-CoA carboxylase(ACCase),hydroxymethylglutaryl coenzyme A(HMG-CoA)reductase in liver,and hormone-sensitive lipase(HSL),and adipose triglyceride lipase(ATGL)in subcutaneous adipose tissue,were measured by real-time PCR.The liver concentrations of triglyceride,reactive oxygen species,and ACCase were measured by ELISA and HSL activity was determined using turbidimetry.Results:NAFLD developed in the CS,HFD,and CS t HFD groups,with the most severe NAFLD being in the CS t HFD group.Serum AST,ALT,and FFA,liver index,and hepatic triglyceride,FFA,and tumor necrosis factor-a were significantly higher in both the CS and CS t HFD groups.However,food intake and ACCase mRNA expression were lower.The mRNA expression of HSL and ATGL in adipose tissue was much higher,and HSL activity was higher in the CS group than in the BC group,and in the CS t HFD group than in the HFD group.Conclusion:We have successfully established two models of stress-induced NAFLD,suggesting stress can induce and aggravate NAFLD by promoting fat mobilization through upregulation of HSL and ATGL.展开更多
[Objectives]To explore the antidepressant effect of Shenwei Ningyu Tablet,a new antidepressant traditional Chinese medicine,on rat chronic stress depression model and mouse tail suspension models.[Methods]Rat chronic ...[Objectives]To explore the antidepressant effect of Shenwei Ningyu Tablet,a new antidepressant traditional Chinese medicine,on rat chronic stress depression model and mouse tail suspension models.[Methods]Rat chronic stress model:except for the normal group,the rats in other groups were given corresponding chronic stress,and administered by gavage 1 h before modeling,for a total of 21 d.The changes of each indicator before and after the experiment were observed through the body weight change,the sugar water test,and open field test.The relevant hormone levels were detected by radioimmunoassay.Mouse tail suspension depression model:after continuous administration for 7 d,the activity times was recorded with the mouse automatic recorder,and the mouse immobility time was recorded after tail suspension,to explore the effects of each administration group on the tail suspension immobility time of mice.[Results]Chronic stress depression model:21 d after modeling,compared with the normal group,rats in the model group exhibited significantly reduced body weight,sucrose preference index,and horizontal and vertical movement scores(P<0.05).Compared with the model group,the low-dose Shenwei Ningyu Tablets group had significant differences in the sugar water test,horizontal and vertical movement scores(P<0.05).In addition,all three dose groups of Shenwei Ningyu Tablets could effectively reduce the content of CRF in chronic stress model rats,and the low dose group could significantly reduce the ACTH level in model rats(P<0.05).Mouse tail suspension depression model:the immobility time after tail suspension in each administration group was significantly different from that in the model group(P<0.05).[Conclusions]Shenwei Ningyu Tablets has a certain anti-depression effect on both the rat chronic stress depression model and the mouse tail suspension depression model.展开更多
Chronic stress can induce hippocampus injury such as neuron loss and dendrite atrophy,but its mechanism and molecular basis remain unclear up to now.To understand the molecular mechanism on protein level and find the ...Chronic stress can induce hippocampus injury such as neuron loss and dendrite atrophy,but its mechanism and molecular basis remain unclear up to now.To understand the molecular mechanism on protein level and find the crucial proteins which correlated with chronic展开更多
Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in ...Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.展开更多
Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous...Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.展开更多
Objective: To evaluate the anti-stress activity of standardized extract of Fumaria indica (FI) through validated beha-vioral models of rodents followed by estimation of biochemical changes associated with chronic stre...Objective: To evaluate the anti-stress activity of standardized extract of Fumaria indica (FI) through validated beha-vioral models of rodents followed by estimation of biochemical changes associated with chronic stress. Methods: Fifty percent ethanolic extract of FI used in this study was standardized on its contents of fumaric acid and its conjugates (0.45% and 0.35% respectively). Stressed Charles Foster rats received unpredictable foot shocks (2 mA, 1 hr, 14 days) through electric grid. FI was given orally as 0.3% carboxymethyl cellulose (CMC) suspension in 100, 200 and 400 mg/kg doses. For comparison, Panax ginseng (PG) extract (100 mg/kg, p.o.) was used as standard adaptogen. Incidence of gastric ulceration, changes in weight of adrenal and spleen, behavioral depression, cognitive dysfunction test and suppression of sexual behavior in male rats were used as validated behavioral models. Plasma corticosterone, brain levels of lipid peroxides (LPO), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), and expression of cytokines IL-1β, TNF-α and IL-10 in circulating white blood cells (WBC) were quantified for ascertaining biochemical changes accompanying stress. Results: As compared to vehicle treated stressed rats, the FI and PG treated rats showed fewer incidence of gastric ulceration, reversal of changes in weight of adrenal gland and spleen, reversal of behavioral depression, better performance in passive and active avoidance tests for cognitive function and increased sexual activity. FI and PG significantly decreased chronic unpredictable stress induced elevation of corticosterone, and both extracts normalized also the abnormal oxidative status of the brain observed in stressed rats. FI treatment also suppressed the elevated level of IL-1β, TNF-α and IL-10 in stressed animals. Conclusions: FI could be another adaptogenic herb and fumaric acid and its conjugates are possibly involved in observed bioactivity of its extract.展开更多
Recent studies have shown that varied stress stimuli activate c-Jun N-terminal kinase(JNK),protein kinase B(Akt),and p38 mitogen-activated protein kinase(p38) signal transduction pathway,and also regulate various apop...Recent studies have shown that varied stress stimuli activate c-Jun N-terminal kinase(JNK),protein kinase B(Akt),and p38 mitogen-activated protein kinase(p38) signal transduction pathway,and also regulate various apoptotic cascades.JNK and p38 promote apoptosis,but Akt protects against apoptosis,in hippocampal neurons.However,changes in the transduction pathway in different regions of brain tissues in a chronic stress rat model of depression remain poorly understood.Results from this study showed that JNK phosphorylation levels were significantly greater in the stress group hippocampus compared with the control group(P < 0.05).No significant difference in JNK phosphorylation levels was detected in the rat cerebral cortex between stress and control groups,and no significant difference in Akt and p38 phosphorylation levels was detected in the rat hippocampus and cerebral cortex between stress and control groups(P > 0.05).These results suggested that the JNK signal pathway is activated by JNK phosphorylation and participates in pathophysiological changes in rat models of depression.展开更多
Objective To observe the effects of chronic emotional stress on the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and malonialdehyde (MDA) level in female rats’ brain. Methods The rats ...Objective To observe the effects of chronic emotional stress on the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and malonialdehyde (MDA) level in female rats’ brain. Methods The rats were randomly divided into 4 groups: normal control group (group N), emotional stress group (group E), emotional stress + pregnancy group (group E+P) and regularly drinking group (group R). Emotional stress in rats was induced by training rats with empty drinking bottles. Having been finished the stress procedure, the brain was taken out and homogenized. Then the activities of SOD, GSH-Px and MDA level were measured. Results Compared to group N, both the activities of SOD in brain tissues of group E and group E+P were significantly decreased ( P <0.05 and P <0.01, respectively) while the MDA level increased ( P <0.05). However, the extent of changes in group E+P was more obvious than that in E. GSH-Px activities in E+P and E were significantly changed. However, the GSH-Px activity in E+P was decreased ( P <0.05) while the activity in E increased ( P <0.05).Conclusion The chronic emotional stress can reduce the antioxidative system by decreasing the antioxidative enzyme activity and potentiating the lipid peroxidation in the brain. It is also suggested that the combination of emotional stress and pregnancy can augment the oxidative damage in rats’ brain.展开更多
To explore chronic heterotypic stressors induced proliferation and activation of mast cells in gastric antrum mucosa by ultrastructure alterations of mast cells,chronic unpredictable heterotypic stressors were used as...To explore chronic heterotypic stressors induced proliferation and activation of mast cells in gastric antrum mucosa by ultrastructure alterations of mast cells,chronic unpredictable heterotypic stressors were used as a study model.The mean immunofluorescence magnitude of mast cell protease 1 (MCP-1) taken from chronic stress rats were 37.4±7.7,significantly higher (p<0.05) than the value of normal control group (24.8±5.6).Chronic unpre-dictable haterotypic stressors appeared also to induce ultrastructure alterations of mast cells.It indicated that mast cells were proliferated and activated,while mast cell granules were hyperplasiaed.Most granules had obvious intragranular changes with loss of electron-dense material.The morphologic evidence showed that macro-phages and leukocytes infiltrated in chronic stress rats.Some granules of leukocytes adhered to the surface of mast cell,and formed a bridge.Macrophages phagocytized the mast cell granules.展开更多
Four weeks of uncertain stress was used to establish an animal model of chronic stress. Basic fibroblast growth factor was injected daily for 15 days following stress induction. Cell morphology in the hippocampal CA3 ...Four weeks of uncertain stress was used to establish an animal model of chronic stress. Basic fibroblast growth factor was injected daily for 15 days following stress induction. Cell morphology in the hippocampal CA3 region of chronic stress mice revealed cell damage. Nitric oxide content and calcium concentration were significantly increased in the hippocampus, and learning and memory functions were significantly decreased. After basic fibroblast growth factor intervention, Ca2+ overload was decreased and neuronal damage was relieved in hippocampal neurons, which improved learning and memory functions in chronic stress mice. Latency was prolonged and the number of errors was decreased in a passive avoidance test.展开更多
Background:Chronic heat stress has a negative impact on poultry meat quality.Although this has been extensively investigated,previous studies have primarily focused on metabolic alterations and oxidative stress in the...Background:Chronic heat stress has a negative impact on poultry meat quality.Although this has been extensively investigated,previous studies have primarily focused on metabolic alterations and oxidative stress in the pectoralis major(PM)muscle under chronic heat stress,and not all of the underlying molecular mechanisms are completely understood.Methods:A total of 144 male Arbor Acres broilers(28 d old)were randomly allocated into 3 treatment groups:(1)the normal control(NC)group,with broilers raised at 22℃and fed a basal diet;(2)the heat stress(HS)group,with birds raised at 32℃and fed a basal diet;and(3)the pair-fed(PF)group,with birds raised at 22℃and fed the amount of feed equal to the feed consumed on the previous day by the HS group.The experiment lasted for 14 d.Results:Chronic heat stress decreased the average daily feed intake and average daily gain,increased feed:gain ratio(P<0.05);and increased drip loss,cooking loss,shear force,hardness,and decreased p H,redness(a*);and springiness of PM muscle(P<0.05).Furthermore,chronic heat stress decreased muscle fiber density,increased connective tissue,and led to intracellular vacuolation.The transcriptome analyses indicated that the effect of chronic heat stress on meat quality was not only related to metabolism and oxidative stress,but also to signal transduction,immune system,transport and catabolism,cell growth and death,and muscle structure.Conclusions:Chronic heat stress has a negative impact on the growth performance,meat quality,and the PM muscle structure of broilers.Transcriptome analysis revealed a comprehensive understanding of the mechanism of the chronic heat stress-induced deterioration of broiler meat quality at the transcriptional level.展开更多
Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like...Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like behaviors is still unclear. This study investigated the effects of SGHWT on metabolic change in the liver and hypothalamus with signaling pathways involved in chronic unpredictable mild stress (CUMS)-induced depression in rats to explore the mechanism of the anti-depressive effect. Methods: A total of 52 rats were used to create a model of depression by CUMS combined with solitary rearing for 6 weeks. Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and body weight (BW) were performed to analyze the pharmacodynamic effects of SGHWT. H&E staining, Nissl staining, immunofluorescence, immunohistochemistry, and western blot were used to evaluate the mechanism of action. Untargeted metabolomics techniques by ultra-performance liquid chromatography-quantitative time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to analyze all the metabolic differences in the liver and hypothalamus. Results: SGHWT improved CUMS-induced depression-like behaviors in vivo. SGHWT reduced hepatic c-Fos protein expression and increased hypothalamic c-Fos protein expression. Moreover, p-PI3K, p-AKT473, p-AKT308, and p-mTOR protein expressions were significantly downregulated in the liver and hypothalamus of CUMS rats. Notably, these alterations were reversed by the SGHWT administration. Furthermore, the metabolomic analysis identified 15 and 5 key differential SPT-associated metabolites in the liver and hypothalamus, respectively. Conclusion: This study suggests that SGHWT ameliorates chronic unpredictable mild stress-induced depression-like behaviors, by the involvement of amino acids, glycerophospholipids, energy metabolism, and the PI3K/AKT/mTOR pathway. Highlights: 1) Shuganheweitang was derived from the TCM herbal formula Sinisan. 2) SGHWT treatment reverses depression-like behaviors in CUMS-induced rats. 3) The mechanism of SGHWT on depression by the liver and hypothalamus metabolomics. 4) SGHWT regulates amino acids, glycerophospholipids, and energy metabolism. 5) SGHWT exerts antidepressant effects through the PI3K/AKT/mTOR pathway.展开更多
Introduction: The goal of this study was to use a novel approach to pain relief which includes a participant using their mind to reduce or relieve their neck pain in a matter of minutes and taking continuous thermal m...Introduction: The goal of this study was to use a novel approach to pain relief which includes a participant using their mind to reduce or relieve their neck pain in a matter of minutes and taking continuous thermal medical imaging scans during the process to capture any concurrent temperature changes at the location of the self-reported pain. Previous studies using multidisciplinary approaches have shown that it is possible for a person to achieve a moderate reduction in pain over a period of time (typically two or more months). However, in this innovative study, the goal was to demonstrate rapid pain relief (in a matter of minutes) using only the mind. Case report: For this study, six subjects were selected, all of whom were experiencing long-term chronic neck pain. The subjects consisted of five adult females and one adult male. Several of the subjects also had pain that radiated into their upper back region. Each subject participated in one talk therapy session during which the subject’s neck was actively scanned by a thermal imaging (TI) camera that was programmed to take a new thermal image every thirty (30) seconds. The goal of the talk therapy session was to create a strong emotional shift by encouraging the subject to let go of negative emotions and replace buried painful feelings with feelings of positive expectation and optimism. Then, as the subject created this emotional shift, the goal was to observe if this change affected the subject’s self-reported physical pain, as well as noting any visible effects in thermal images. Results: All six subjects reported that they were able to relieve some or all of their pain by the end of the talk therapy session. As they did, there was simultaneously a significant decrease in temperature recorded on the TI images in the corresponding location in their neck and upper back region. This suggested that the pain relief the subjects reported was not merely “mind over matter”, since there were marked physiological changes taking place. Discussion and Conclusion: It’s worth noting that three of the subjects had moments during their talk therapy session where they thought about a specific painful memory that increased their negative emotions. At that moment, their self-reported pain also increased, and simultaneously, the infrared camera detected an increase in temperature in the corresponding location where the subjects reported increased pain. Subsequently, when the subjects were able to change the painful memory and once again move towards feelings of optimism, they reported pain relief, and simultaneously, the TI camera reported a decrease in temperature. Neither this potential outcome nor any other potential outcome was discussed with the subjects before or during the session. This research shows that talk therapy may be used as a new therapeutic option for people not only with neck pain, but possibly other types of pain, and that under certain circumstances, the results can be rapid.展开更多
Chronic stress plays a critical role in the etiology of sporadic Alzheimer's disease(AD).However,there are currently no effective drugs that can target chronic stress to prevent AD.In this study,we explored the ne...Chronic stress plays a critical role in the etiology of sporadic Alzheimer's disease(AD).However,there are currently no effective drugs that can target chronic stress to prevent AD.In this study,we explored the neuroprotective effect of hydroxysafflor yellow A(HSYA)against chronic mild stress(CMS)-induced memory impairments in mice and the underlying mechanism.The Morris water maze test showed that HSYA significantly reduced CMS-induced learning and memory impairments in mice.HSYA increased the expression of brain-derived neurotrophic factor(BDNF)and activated downstream tropomyosin-related kinase B(TrkB)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling.HSYA decreased the expression of regulator of calcineurin 1-1L(RCAN1-1L)that could promote the activity of glycogen synthase kinase-3β(GSK-3β).HSYA also attenuated tau phosphorylation by inhibiting the activity of GSK-3βand cyclin-dependent kinase-5(Cdk5).Our data indicated that HSYA has protective effects against CMS-induced BDNF downregulation,tau phosphorylation and memory impairments.HSYA may be a promising therapeutic candidate for AD by targeting chronic stress.展开更多
Background:Gut microbiota can interact with the central nervous system through the gut-brain axis,thus affecting the host’s chronic stress level,such as anxiety and depression.Current researches show that patients wi...Background:Gut microbiota can interact with the central nervous system through the gut-brain axis,thus affecting the host’s chronic stress level,such as anxiety and depression.Current researches show that patients with endometriosis often have a high level of chronic stress,which will in turn aggravate endometriosis by activating theβ-adrenergic signaling pathway.Therefore,we wondered whether the gut microbiota associates with the chronic stress level in endometriosis patients,which may provide new insights on how to improve treatment.Methods:We grouped the endometriosis patients into the chronic stress group and the control group with questionnaires such as generalized anxiety disorder-7 and patient health questionnaire-9 and collected patients’fecal specimens and tissue specimens.Gut microbiota compositions were analyzed by the 16SrRNA gene sequencing-based method,and immunohistochemistry was performed to detect the activation of inflammatory pathways in endometriosis tissues.Results:We found that in patients with endometriosis,the dysbiosis of gut microbiota was associated with their stress levels.Furthermore,the levels of Paraprevotella,Odoribacter,Veillonella,and Ruminococcus were significantly reduced in chronic stressed endometriosis patients,suggestive of a disease-specific change of gut microbiota at the genus level.Compared to the healthy women,the expression levels of inflammatory cytokines,nuclear factor-κB p65,and cyclooxygenase-2 increased in the chronic stressed endometriosis patients,indicating that the dysbiosis of gut microbiota may activate the inflammatory pathway of gut-brain axis.Conclusions:We hypothesized that these new disease-specific changes of gut microbiota in chronic stressed patients with endometriosis may be a new examination target of chronic stress level.These changes may also provide new insights for psychological intervention,thus reducing the stress level and improving the prognosis of endometriosis patients.展开更多
Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows...Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows:the normal saline group(control,n=10),the daily stress group(daily stress,n=10),the baicalein group(baicalein,n=10),and the daily stress+baicalein group(daily stress+baicalein,n=10).For the daily stress model,we used a restricted stress model.Baicalein(10 mg/kg)was administered by gavage every day,and control mice received normal saline equivalently.Biopsy specimens were harvested after 4 weeks.Measurement of norepinephrine(NE)in serum was performed to assess the psychological stress level of the mice.In addition,histological changes of the uterus and ovaries and the levels of anti-Müllerian hormone(AMH)in serum were assessed to evaluate changes in ovarian function.To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction,immunohistochemical methods,and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid(GABA)receptors.Results:Compared with values in the control group,serum NE concentrations were significantly increased(P<0.001),AMH concentrations were markedly decreased(P<0.01),the thickness of the endometrium was clearly reduced,and the percentage of atretic follicles was significantly increased in the daily stress group(P<0.001),indicating that the chronic stress model was successfully established.In contrast,compared with values in the daily stress group,serum NE concentrations were significantly reduced(P<0.001),AMH concentrations were significantly enhanced(P<0.05),the thickness of the endometrium was clearly increased,and the percentage of atretic follicles was significantly reduced(P<0.001)in the daily stress+baicalein group,indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress.Moreover,the expression of the GABAB2 receptor in the daily stress group was significantly reduced(P<0.01).In contrast,treatment with baicalein resulted in increased expression of the GABAB2 receptor(P<0.01).Conclusions:Treatment with baicalein ameliorates the enhancing effect of chronic stress on ovarian dysfunction,and the mechanism can be attributed,in part,to the increased expression of the GABAB2 receptor.展开更多
AIM:To investigate the effect of Simotang(Decoction of Four Powered Drugs) on gastrointestinal motility,motilin and cholecystokinin expression in chronically stressed mice.METHODS:Forty mice were randomly divided into...AIM:To investigate the effect of Simotang(Decoction of Four Powered Drugs) on gastrointestinal motility,motilin and cholecystokinin expression in chronically stressed mice.METHODS:Forty mice were randomly divided into control group,stress group(model group),mosapride group and Simotang group,10 in each group.A variety of unpredictable stimulations were used to induce chronic stress in mice.Then,the mice were treated with distilled water,mosapride or Simotang for 7 d.Gastric emptying and intestinal propulsion function were detected.Serum level of motilin was measured by enzyme-linked immunosorbent assay.Expression of cholecystokinin(CCK) in intestine,spinal cord and brain of mice was detected by immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction,respectively.RESULTS:Simotang improved the gastric emptying and intestinal propulsion in chronically stressed mice.Furthermore,the serum motilin level was significantly higher and the expression levels of CCK-positive cells and genes were significantly lower in intestine,spinal cord and brain of Simotang group than in those of model group(P<0.05).No significant difference was found in serum motilin level and expression levels of CCK-positive cells and genes between the mosapride and Simotang groups.CONCLUSION:Simotang enhances the gastrointestinal motility in chronically stressed mice by regulating the serum motilin level and the expression of cholecystokinin.展开更多
基金supported by the National Natural Science Foundation of China(81373584)。
文摘Objective:To explore the mechanism of the Peiyuan Jieyu formula in treating depression by assessing its impact on a lipopolysaccharide-induced(LPS-induced)depression mouse model.Methods:We created a mouse model of depression by exposing mice that had previously received chronic stress to intraperitoneal LPS injections.The mice were divided into the following groups:control,model,fluoxetine,Tiansi Yin,Sini powder,and low-,medium-,and high-dose Peiyuan Jieyu formula groups.Forced swim and tail suspension tests were used to assess the efficacy of the depression(despair)model,and weight gain rates were also measured.Furthermore,serum levels of various depression and inflammation-associated molecules,including tumor necrosis factor-a(TNF-a),interferon-γ(IFN-γ),tryptophan,5-hydroxytryptamine,kynurenine(KYN),and kynurenic acid(KA)were assessed.Furthermore,the expression levels of ionic calcium-binding adaptor molecule-1(IBA-1)and indoleamine 2,3-dioxygenase(IDO)mRNA in hippocampal microglia were measured.Results:The model group displayed greater despair-associated immobility,which was shortened in response to various doses of Peiyuan Jieyu formula.Furthermore,formula administration significantly reduced serum TNF-a levels and hippocampal IDO mRNA expression.The high formula dose also reduced IFN-γand IBA-1 levels,the latter was also decreased in response to the medium formula dose.However,the low formula dose reduced serum KYN level and KYN/tryptophan(TRP)and KYN/KA ratios.Conclusion:The Peiyuan Jieyu formula holds immense potential in treating depression in a mouse model,potentially inhibiting inflammation and improving TRP-KYN metabolic disorders.
基金This work was supported by the National Natural Science Foundation of China Surface Project(81774122)Young Teachers Project of Beijing University of Chinese Medicine(2017-JYB-JS-002)University Level Project of Beijing University of Chinese Medicine(2019-JYB-XS-002).
文摘Objective:To study the effects of social stress(CS)and social stress combined with high-fat diet on fat mobilization as a candidate mechanism for the induction or aggravation of non-alcoholic fatty liver disease(NAFLD).Methods:Thirty-two male Wistar rats(250±10 g)were randomly allocated to a blank control group(BC),a high-fat diet group(HFD),a CS group,and a combined CS and high-fat diet group(CS t HFD).Rats were sacrificed and tissues were collected after 8 weeks.Liver and body mass were measured and used to calculate the liver index.Serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),and free fatty acids(FFAs)were measured.Liver sections were examined microscopically after oil red O and hematoxylin and eosin staining.The relative mRNA expression of acetyl-CoA carboxylase(ACCase),hydroxymethylglutaryl coenzyme A(HMG-CoA)reductase in liver,and hormone-sensitive lipase(HSL),and adipose triglyceride lipase(ATGL)in subcutaneous adipose tissue,were measured by real-time PCR.The liver concentrations of triglyceride,reactive oxygen species,and ACCase were measured by ELISA and HSL activity was determined using turbidimetry.Results:NAFLD developed in the CS,HFD,and CS t HFD groups,with the most severe NAFLD being in the CS t HFD group.Serum AST,ALT,and FFA,liver index,and hepatic triglyceride,FFA,and tumor necrosis factor-a were significantly higher in both the CS and CS t HFD groups.However,food intake and ACCase mRNA expression were lower.The mRNA expression of HSL and ATGL in adipose tissue was much higher,and HSL activity was higher in the CS group than in the BC group,and in the CS t HFD group than in the HFD group.Conclusion:We have successfully established two models of stress-induced NAFLD,suggesting stress can induce and aggravate NAFLD by promoting fat mobilization through upregulation of HSL and ATGL.
基金National Major Scientific and Technological Special Project for"Significant New Drugs Development"(2019ZX09301-005).
文摘[Objectives]To explore the antidepressant effect of Shenwei Ningyu Tablet,a new antidepressant traditional Chinese medicine,on rat chronic stress depression model and mouse tail suspension models.[Methods]Rat chronic stress model:except for the normal group,the rats in other groups were given corresponding chronic stress,and administered by gavage 1 h before modeling,for a total of 21 d.The changes of each indicator before and after the experiment were observed through the body weight change,the sugar water test,and open field test.The relevant hormone levels were detected by radioimmunoassay.Mouse tail suspension depression model:after continuous administration for 7 d,the activity times was recorded with the mouse automatic recorder,and the mouse immobility time was recorded after tail suspension,to explore the effects of each administration group on the tail suspension immobility time of mice.[Results]Chronic stress depression model:21 d after modeling,compared with the normal group,rats in the model group exhibited significantly reduced body weight,sucrose preference index,and horizontal and vertical movement scores(P<0.05).Compared with the model group,the low-dose Shenwei Ningyu Tablets group had significant differences in the sugar water test,horizontal and vertical movement scores(P<0.05).In addition,all three dose groups of Shenwei Ningyu Tablets could effectively reduce the content of CRF in chronic stress model rats,and the low dose group could significantly reduce the ACTH level in model rats(P<0.05).Mouse tail suspension depression model:the immobility time after tail suspension in each administration group was significantly different from that in the model group(P<0.05).[Conclusions]Shenwei Ningyu Tablets has a certain anti-depression effect on both the rat chronic stress depression model and the mouse tail suspension depression model.
文摘Chronic stress can induce hippocampus injury such as neuron loss and dendrite atrophy,but its mechanism and molecular basis remain unclear up to now.To understand the molecular mechanism on protein level and find the crucial proteins which correlated with chronic
基金a grant from Science and Technology Bureau of Beijing, No.Z090507017709030
文摘Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.
基金supported by the National Natural Science Foundation of China,No.30370537
文摘Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.
文摘Objective: To evaluate the anti-stress activity of standardized extract of Fumaria indica (FI) through validated beha-vioral models of rodents followed by estimation of biochemical changes associated with chronic stress. Methods: Fifty percent ethanolic extract of FI used in this study was standardized on its contents of fumaric acid and its conjugates (0.45% and 0.35% respectively). Stressed Charles Foster rats received unpredictable foot shocks (2 mA, 1 hr, 14 days) through electric grid. FI was given orally as 0.3% carboxymethyl cellulose (CMC) suspension in 100, 200 and 400 mg/kg doses. For comparison, Panax ginseng (PG) extract (100 mg/kg, p.o.) was used as standard adaptogen. Incidence of gastric ulceration, changes in weight of adrenal and spleen, behavioral depression, cognitive dysfunction test and suppression of sexual behavior in male rats were used as validated behavioral models. Plasma corticosterone, brain levels of lipid peroxides (LPO), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH), and expression of cytokines IL-1β, TNF-α and IL-10 in circulating white blood cells (WBC) were quantified for ascertaining biochemical changes accompanying stress. Results: As compared to vehicle treated stressed rats, the FI and PG treated rats showed fewer incidence of gastric ulceration, reversal of changes in weight of adrenal gland and spleen, reversal of behavioral depression, better performance in passive and active avoidance tests for cognitive function and increased sexual activity. FI and PG significantly decreased chronic unpredictable stress induced elevation of corticosterone, and both extracts normalized also the abnormal oxidative status of the brain observed in stressed rats. FI treatment also suppressed the elevated level of IL-1β, TNF-α and IL-10 in stressed animals. Conclusions: FI could be another adaptogenic herb and fumaric acid and its conjugates are possibly involved in observed bioactivity of its extract.
基金the General Program of National Natural Science Foundation of China, No.90709034
文摘Recent studies have shown that varied stress stimuli activate c-Jun N-terminal kinase(JNK),protein kinase B(Akt),and p38 mitogen-activated protein kinase(p38) signal transduction pathway,and also regulate various apoptotic cascades.JNK and p38 promote apoptosis,but Akt protects against apoptosis,in hippocampal neurons.However,changes in the transduction pathway in different regions of brain tissues in a chronic stress rat model of depression remain poorly understood.Results from this study showed that JNK phosphorylation levels were significantly greater in the stress group hippocampus compared with the control group(P < 0.05).No significant difference in JNK phosphorylation levels was detected in the rat cerebral cortex between stress and control groups,and no significant difference in Akt and p38 phosphorylation levels was detected in the rat hippocampus and cerebral cortex between stress and control groups(P > 0.05).These results suggested that the JNK signal pathway is activated by JNK phosphorylation and participates in pathophysiological changes in rat models of depression.
文摘Objective To observe the effects of chronic emotional stress on the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and malonialdehyde (MDA) level in female rats’ brain. Methods The rats were randomly divided into 4 groups: normal control group (group N), emotional stress group (group E), emotional stress + pregnancy group (group E+P) and regularly drinking group (group R). Emotional stress in rats was induced by training rats with empty drinking bottles. Having been finished the stress procedure, the brain was taken out and homogenized. Then the activities of SOD, GSH-Px and MDA level were measured. Results Compared to group N, both the activities of SOD in brain tissues of group E and group E+P were significantly decreased ( P <0.05 and P <0.01, respectively) while the MDA level increased ( P <0.05). However, the extent of changes in group E+P was more obvious than that in E. GSH-Px activities in E+P and E were significantly changed. However, the GSH-Px activity in E+P was decreased ( P <0.05) while the activity in E increased ( P <0.05).Conclusion The chronic emotional stress can reduce the antioxidative system by decreasing the antioxidative enzyme activity and potentiating the lipid peroxidation in the brain. It is also suggested that the combination of emotional stress and pregnancy can augment the oxidative damage in rats’ brain.
基金the Fund of Stanley Medical Reseach Institute of American (02I-002)
文摘To explore chronic heterotypic stressors induced proliferation and activation of mast cells in gastric antrum mucosa by ultrastructure alterations of mast cells,chronic unpredictable heterotypic stressors were used as a study model.The mean immunofluorescence magnitude of mast cell protease 1 (MCP-1) taken from chronic stress rats were 37.4±7.7,significantly higher (p<0.05) than the value of normal control group (24.8±5.6).Chronic unpre-dictable haterotypic stressors appeared also to induce ultrastructure alterations of mast cells.It indicated that mast cells were proliferated and activated,while mast cell granules were hyperplasiaed.Most granules had obvious intragranular changes with loss of electron-dense material.The morphologic evidence showed that macro-phages and leukocytes infiltrated in chronic stress rats.Some granules of leukocytes adhered to the surface of mast cell,and formed a bridge.Macrophages phagocytized the mast cell granules.
基金the "Eleventh Five-Year" Scientific and Technological Research Projects of the Education Department of Jilin Province, No. [2008]137
文摘Four weeks of uncertain stress was used to establish an animal model of chronic stress. Basic fibroblast growth factor was injected daily for 15 days following stress induction. Cell morphology in the hippocampal CA3 region of chronic stress mice revealed cell damage. Nitric oxide content and calcium concentration were significantly increased in the hippocampus, and learning and memory functions were significantly decreased. After basic fibroblast growth factor intervention, Ca2+ overload was decreased and neuronal damage was relieved in hippocampal neurons, which improved learning and memory functions in chronic stress mice. Latency was prolonged and the number of errors was decreased in a passive avoidance test.
基金the National Natural Science Foundation of China(32072780,31872374)the National Key Research and Development Program of China(2016YFD0500501,2018YFD0500405)the Earmarked Fund for Jiangsu Agricultural Industry Technology System(JATS[2021]459)。
文摘Background:Chronic heat stress has a negative impact on poultry meat quality.Although this has been extensively investigated,previous studies have primarily focused on metabolic alterations and oxidative stress in the pectoralis major(PM)muscle under chronic heat stress,and not all of the underlying molecular mechanisms are completely understood.Methods:A total of 144 male Arbor Acres broilers(28 d old)were randomly allocated into 3 treatment groups:(1)the normal control(NC)group,with broilers raised at 22℃and fed a basal diet;(2)the heat stress(HS)group,with birds raised at 32℃and fed a basal diet;and(3)the pair-fed(PF)group,with birds raised at 22℃and fed the amount of feed equal to the feed consumed on the previous day by the HS group.The experiment lasted for 14 d.Results:Chronic heat stress decreased the average daily feed intake and average daily gain,increased feed:gain ratio(P<0.05);and increased drip loss,cooking loss,shear force,hardness,and decreased p H,redness(a*);and springiness of PM muscle(P<0.05).Furthermore,chronic heat stress decreased muscle fiber density,increased connective tissue,and led to intracellular vacuolation.The transcriptome analyses indicated that the effect of chronic heat stress on meat quality was not only related to metabolism and oxidative stress,but also to signal transduction,immune system,transport and catabolism,cell growth and death,and muscle structure.Conclusions:Chronic heat stress has a negative impact on the growth performance,meat quality,and the PM muscle structure of broilers.Transcriptome analysis revealed a comprehensive understanding of the mechanism of the chronic heat stress-induced deterioration of broiler meat quality at the transcriptional level.
文摘Background: Depression is a typical psychosomatic disease. Shuganheweitang (SGHWT) is a clinical formula that effectively treats depression. However, the potential mechanism used by SGHWT to ameliorate depression-like behaviors is still unclear. This study investigated the effects of SGHWT on metabolic change in the liver and hypothalamus with signaling pathways involved in chronic unpredictable mild stress (CUMS)-induced depression in rats to explore the mechanism of the anti-depressive effect. Methods: A total of 52 rats were used to create a model of depression by CUMS combined with solitary rearing for 6 weeks. Open field test (OFT), sucrose preference test (SPT), forced swim test (FST), and body weight (BW) were performed to analyze the pharmacodynamic effects of SGHWT. H&E staining, Nissl staining, immunofluorescence, immunohistochemistry, and western blot were used to evaluate the mechanism of action. Untargeted metabolomics techniques by ultra-performance liquid chromatography-quantitative time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to analyze all the metabolic differences in the liver and hypothalamus. Results: SGHWT improved CUMS-induced depression-like behaviors in vivo. SGHWT reduced hepatic c-Fos protein expression and increased hypothalamic c-Fos protein expression. Moreover, p-PI3K, p-AKT473, p-AKT308, and p-mTOR protein expressions were significantly downregulated in the liver and hypothalamus of CUMS rats. Notably, these alterations were reversed by the SGHWT administration. Furthermore, the metabolomic analysis identified 15 and 5 key differential SPT-associated metabolites in the liver and hypothalamus, respectively. Conclusion: This study suggests that SGHWT ameliorates chronic unpredictable mild stress-induced depression-like behaviors, by the involvement of amino acids, glycerophospholipids, energy metabolism, and the PI3K/AKT/mTOR pathway. Highlights: 1) Shuganheweitang was derived from the TCM herbal formula Sinisan. 2) SGHWT treatment reverses depression-like behaviors in CUMS-induced rats. 3) The mechanism of SGHWT on depression by the liver and hypothalamus metabolomics. 4) SGHWT regulates amino acids, glycerophospholipids, and energy metabolism. 5) SGHWT exerts antidepressant effects through the PI3K/AKT/mTOR pathway.
文摘Introduction: The goal of this study was to use a novel approach to pain relief which includes a participant using their mind to reduce or relieve their neck pain in a matter of minutes and taking continuous thermal medical imaging scans during the process to capture any concurrent temperature changes at the location of the self-reported pain. Previous studies using multidisciplinary approaches have shown that it is possible for a person to achieve a moderate reduction in pain over a period of time (typically two or more months). However, in this innovative study, the goal was to demonstrate rapid pain relief (in a matter of minutes) using only the mind. Case report: For this study, six subjects were selected, all of whom were experiencing long-term chronic neck pain. The subjects consisted of five adult females and one adult male. Several of the subjects also had pain that radiated into their upper back region. Each subject participated in one talk therapy session during which the subject’s neck was actively scanned by a thermal imaging (TI) camera that was programmed to take a new thermal image every thirty (30) seconds. The goal of the talk therapy session was to create a strong emotional shift by encouraging the subject to let go of negative emotions and replace buried painful feelings with feelings of positive expectation and optimism. Then, as the subject created this emotional shift, the goal was to observe if this change affected the subject’s self-reported physical pain, as well as noting any visible effects in thermal images. Results: All six subjects reported that they were able to relieve some or all of their pain by the end of the talk therapy session. As they did, there was simultaneously a significant decrease in temperature recorded on the TI images in the corresponding location in their neck and upper back region. This suggested that the pain relief the subjects reported was not merely “mind over matter”, since there were marked physiological changes taking place. Discussion and Conclusion: It’s worth noting that three of the subjects had moments during their talk therapy session where they thought about a specific painful memory that increased their negative emotions. At that moment, their self-reported pain also increased, and simultaneously, the infrared camera detected an increase in temperature in the corresponding location where the subjects reported increased pain. Subsequently, when the subjects were able to change the painful memory and once again move towards feelings of optimism, they reported pain relief, and simultaneously, the TI camera reported a decrease in temperature. Neither this potential outcome nor any other potential outcome was discussed with the subjects before or during the session. This research shows that talk therapy may be used as a new therapeutic option for people not only with neck pain, but possibly other types of pain, and that under certain circumstances, the results can be rapid.
基金the Fundamental Research Funds for the Central Universities(No.lzujbky-2016-70)the Natural Science Foundation of Gansu Province(No.1506RJZA235).
文摘Chronic stress plays a critical role in the etiology of sporadic Alzheimer's disease(AD).However,there are currently no effective drugs that can target chronic stress to prevent AD.In this study,we explored the neuroprotective effect of hydroxysafflor yellow A(HSYA)against chronic mild stress(CMS)-induced memory impairments in mice and the underlying mechanism.The Morris water maze test showed that HSYA significantly reduced CMS-induced learning and memory impairments in mice.HSYA increased the expression of brain-derived neurotrophic factor(BDNF)and activated downstream tropomyosin-related kinase B(TrkB)and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling.HSYA decreased the expression of regulator of calcineurin 1-1L(RCAN1-1L)that could promote the activity of glycogen synthase kinase-3β(GSK-3β).HSYA also attenuated tau phosphorylation by inhibiting the activity of GSK-3βand cyclin-dependent kinase-5(Cdk5).Our data indicated that HSYA has protective effects against CMS-induced BDNF downregulation,tau phosphorylation and memory impairments.HSYA may be a promising therapeutic candidate for AD by targeting chronic stress.
基金This work was supported by the National Key R&D Program of China(2016YFC1303100)the National Natural Science Foundation of China(81472423)+1 种基金Shanghai Medical Center of Key Programs for Female Reproductive Diseases(2017ZZ01016)Shanghai Municipal Health and Family Planning Commission(ZYKC201701020).
文摘Background:Gut microbiota can interact with the central nervous system through the gut-brain axis,thus affecting the host’s chronic stress level,such as anxiety and depression.Current researches show that patients with endometriosis often have a high level of chronic stress,which will in turn aggravate endometriosis by activating theβ-adrenergic signaling pathway.Therefore,we wondered whether the gut microbiota associates with the chronic stress level in endometriosis patients,which may provide new insights on how to improve treatment.Methods:We grouped the endometriosis patients into the chronic stress group and the control group with questionnaires such as generalized anxiety disorder-7 and patient health questionnaire-9 and collected patients’fecal specimens and tissue specimens.Gut microbiota compositions were analyzed by the 16SrRNA gene sequencing-based method,and immunohistochemistry was performed to detect the activation of inflammatory pathways in endometriosis tissues.Results:We found that in patients with endometriosis,the dysbiosis of gut microbiota was associated with their stress levels.Furthermore,the levels of Paraprevotella,Odoribacter,Veillonella,and Ruminococcus were significantly reduced in chronic stressed endometriosis patients,suggestive of a disease-specific change of gut microbiota at the genus level.Compared to the healthy women,the expression levels of inflammatory cytokines,nuclear factor-κB p65,and cyclooxygenase-2 increased in the chronic stressed endometriosis patients,indicating that the dysbiosis of gut microbiota may activate the inflammatory pathway of gut-brain axis.Conclusions:We hypothesized that these new disease-specific changes of gut microbiota in chronic stressed patients with endometriosis may be a new examination target of chronic stress level.These changes may also provide new insights for psychological intervention,thus reducing the stress level and improving the prognosis of endometriosis patients.
基金supported by the Shanghai Science&Technology Commission(18140902502)the National Key Research and Development Program of China(2016YFC1303100)+2 种基金the National Natural Science Foundation of China(81472423)the Shanghai Clinical and Medical Center of Key Program(2017ZZ01016)the Shanghai Science and Technology Innovation Project of Traditional Chinese Medicine(ZYKC201701020).
文摘Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows:the normal saline group(control,n=10),the daily stress group(daily stress,n=10),the baicalein group(baicalein,n=10),and the daily stress+baicalein group(daily stress+baicalein,n=10).For the daily stress model,we used a restricted stress model.Baicalein(10 mg/kg)was administered by gavage every day,and control mice received normal saline equivalently.Biopsy specimens were harvested after 4 weeks.Measurement of norepinephrine(NE)in serum was performed to assess the psychological stress level of the mice.In addition,histological changes of the uterus and ovaries and the levels of anti-Müllerian hormone(AMH)in serum were assessed to evaluate changes in ovarian function.To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction,immunohistochemical methods,and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid(GABA)receptors.Results:Compared with values in the control group,serum NE concentrations were significantly increased(P<0.001),AMH concentrations were markedly decreased(P<0.01),the thickness of the endometrium was clearly reduced,and the percentage of atretic follicles was significantly increased in the daily stress group(P<0.001),indicating that the chronic stress model was successfully established.In contrast,compared with values in the daily stress group,serum NE concentrations were significantly reduced(P<0.001),AMH concentrations were significantly enhanced(P<0.05),the thickness of the endometrium was clearly increased,and the percentage of atretic follicles was significantly reduced(P<0.001)in the daily stress+baicalein group,indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress.Moreover,the expression of the GABAB2 receptor in the daily stress group was significantly reduced(P<0.01).In contrast,treatment with baicalein resulted in increased expression of the GABAB2 receptor(P<0.01).Conclusions:Treatment with baicalein ameliorates the enhancing effect of chronic stress on ovarian dysfunction,and the mechanism can be attributed,in part,to the increased expression of the GABAB2 receptor.
基金Supported by The National Key Basic Research(973) Program, No.2009CB523002the Hunan Provincial TCM Research Fund,China,No.209004
文摘AIM:To investigate the effect of Simotang(Decoction of Four Powered Drugs) on gastrointestinal motility,motilin and cholecystokinin expression in chronically stressed mice.METHODS:Forty mice were randomly divided into control group,stress group(model group),mosapride group and Simotang group,10 in each group.A variety of unpredictable stimulations were used to induce chronic stress in mice.Then,the mice were treated with distilled water,mosapride or Simotang for 7 d.Gastric emptying and intestinal propulsion function were detected.Serum level of motilin was measured by enzyme-linked immunosorbent assay.Expression of cholecystokinin(CCK) in intestine,spinal cord and brain of mice was detected by immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction,respectively.RESULTS:Simotang improved the gastric emptying and intestinal propulsion in chronically stressed mice.Furthermore,the serum motilin level was significantly higher and the expression levels of CCK-positive cells and genes were significantly lower in intestine,spinal cord and brain of Simotang group than in those of model group(P<0.05).No significant difference was found in serum motilin level and expression levels of CCK-positive cells and genes between the mosapride and Simotang groups.CONCLUSION:Simotang enhances the gastrointestinal motility in chronically stressed mice by regulating the serum motilin level and the expression of cholecystokinin.
