Dear editor,Acute massive pulmonary embolism(PE) is a common life-threatening disease with high mortality of up to 30%–50%.[1,2]Potential heterogeneous reasons for PE remain controversial, and its treatment strategie...Dear editor,Acute massive pulmonary embolism(PE) is a common life-threatening disease with high mortality of up to 30%–50%.[1,2]Potential heterogeneous reasons for PE remain controversial, and its treatment strategies mainly include antithrombotics, fibrinolytics, and embolectomy.展开更多
BACKGROUND： Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome （ARDS） including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortalit...BACKGROUND： Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome （ARDS） including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortality. The objective of this study is to evaluate the effects of dynamic ventilatory factors on ventilator induced lung injury in a dog model of ARDS induced by hydrochloric acid instillation under volume controlled ventilation and to investigate the relationship between the dynamic factors and ventilator-induced lung injuries （VILI） and to explore its potential mechanisms.METHODS： Thirty-six healthy dogs were randomly divided into a control group and an experimental group. Subjects in the experimental group were then further divided into four groups by different inspiratory stages of flow. Two mL of alveolar fluid was aspirated for detection of IL-8 and TNF-α. Lung tissue specimens were also extracted for total RNA, IL-8 by western blot and observed under an electronic microscope.RESULTS： IL-8 protein expression was significantly higher in group B than in groups A and D. Although the IL-8 protein expression was decreased in group C compared with group B, the difference was not statistically significant. The TNF-a ray degree of group B was significantly higher than that in the other groups （P〈0.01）, especially in group C （P〉0.05）. The alveolar volume of subjects in group B was significantly smaller, and cavity infiltration and cell autolysis were marked with a significant thicker alveolar septa, disorder of interval structures, and blurring of collagenous and elastic fiber structures. A large number of necrotic debris tissue was observed in group B.CONCLUSION： Mechanical ventilation with a large tidal volume, a high inspiratory flow and a high ventilation frequency can cause significant damage to lung tissue structure. It can significantly increase the expression of TNF-α and IL-8 as well as their mRNA expression. Furthermore, the results of our study showed that small tidal ventilation significantly reduces the release of proinflammatory media. This finding suggests that greater deterioration in lung injury during ARDS is associated with high inspiratory flow and high ventilation rate.展开更多
AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to ...AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.8 folds vs 59.6±11.6 folds,P<0.01),ZO-1(46±18 folds vs68±19 folds,P<0.01),and E-cadherin proteins(48±15 folds vs 77±18 folds,P<0.01)were underexpressed in SAP intestinal epithelia although RhoA mRNA expression was not significantly changed in SAP(0.97±0.18 folds vs 1.01±0.17 folds,P>0.05).CONCLUSION:TNF-α-regulated miR-155 overexpression inhibits AJC component protein syntheses of ZO-1,and E-cadherin by downregulating post-transcriptional RhoA expression,and disrupts intestinal epithelial barrier in experimental SAP.展开更多
BACKGROUND: Data on the mechanical ventilation(MV) characteristics and radiologic features for the cases with H7 N9-induced ARDS were still lacking.METHODS: We describe the MV characteristics and radiologic features o...BACKGROUND: Data on the mechanical ventilation(MV) characteristics and radiologic features for the cases with H7 N9-induced ARDS were still lacking.METHODS: We describe the MV characteristics and radiologic features of adult patients with ARDS due to microbiologically confirmed H7 N9 admitted to our ICU over a 3-month period.RESULTS: Eight patients(mean age 57.38±16.75; 5 male) were diagnosed with H7 N9 in the first quarter of 2014. All developed respiratory failure complicated by acute respiratory distress syndrome(ARDS), which required MV in ICU. The baseline APACHE II and SOFA score was 11.77±6.32 and 7.71±3.12. The overall CT scores of the patients was 247.68±34.28 and the range of CT scores was 196.3–294.7. The average MV days was 14.63±6.14, and 4 patients required additional rescue therapies for refractory hypoxemia. Despite these measures, 3 patients died.CONCLUSION: In H7 N9-infected patients with ARDS, low tidal volume strategy was the conventional mode. RM as one of rescue therapies to refractory hypoxemia in these patients with serious architectural distortion and high CT scores, which could cause further lung damage, may induce bad outcomes and requires serious consideration. Prone ventilation may improve mortality, and should be performed at the early stage of the disease, not as a rescue therapy.展开更多
BACKGROUND： Ulinastatin （UTI） is a urinary trypsin inhibitor extracted and purified from urine of males. This study aimed to explore the effects of UTI on paraquat-induced-oxidative stress in human type II alveolar...BACKGROUND： Ulinastatin （UTI） is a urinary trypsin inhibitor extracted and purified from urine of males. This study aimed to explore the effects of UTI on paraquat-induced-oxidative stress in human type II alveolar epithelial cells. METHODS： The human type II alveolar epithelial cells, A549 cells, were cultured in vitro. The A549 cells were treated with different concentrations of paraquat （200, 400, 600, 800, 1 000, 1 200 pmol/L） and ulinastatin（0, 2 000, 4 000, 6 000, 8 000 U/mL） for 24 hours, the cell viability was measured by cell counting kit-8 and the median lethal concentration was selected. In order to establish an in vitro model of paraquat intoxication and to determine the safe dose of ulinastatin, we calculated LD50 using cell counting kit-8 to determine the survival rate of the cells. A549 cells were divided into normal control group, paraquat group and paraquat＋ulinastatin group. The levels of malondialdehyde （MDA） and myeloperoxidase （MPO） were detected by biochemistry colorimetry, while the level of reactive oxygen spies （ROS） was detected by DCFH-DA assay. RESULTS： The survival rate of A549 cells treated with different concentrations of paraquat decreased in a concentration-dependent manner. Whereas there was no decrease in the survival rate of cells treated with 0-4 000 U/mL ulinastatin. The levels of MDA, MPO, and ROS were significantly higher in the paraquat group than in the normal control group after 24-hour-exposure. And the survival rate of the paraquat＋ulinastatin group was higher than that of the paraquat group, but lower than that of the normal control group. The levels of MDA, MPO, and ROS were lower than those of the paraquat group. CONCLUSION： Ulinastatin can alleviate the paraquat-induced A549 cell damage by reducing oxidative stress.展开更多
Introduction Human serum albumin(HSA)is a non-glycosylated,negatively charged,single-chain polypeptide composed of 585 amino acid residues with a relative molecular mass of 66.438 kD.It is synthesized by the liver at ...Introduction Human serum albumin(HSA)is a non-glycosylated,negatively charged,single-chain polypeptide composed of 585 amino acid residues with a relative molecular mass of 66.438 kD.It is synthesized by the liver at a rate of approximately 200 mg·kg^(-1)·day^(-1),with a half-life of 21 days,and subjected to catabolism in the muscles,liver,and kidneys at a rate of 4%per day.[1]Albumin,accounting for 60%of the total plasma protein,has various physiological functions,[2]such as maintaining 70%to 80%of effective plasma colloid osmotic pressure,coordinating vascular endothelial integrity,anti-oxidant and anti-inflammatory activities,maintaining the acidbase balance,and participating in the transport,distribution,and metabolism of a variety of endogenous and exogenous substances.展开更多
Background：Acute kidney injury （AKI） is a severe disease in critically ill patients.Neutrophil infiltration into kidney was associated with the development of AKI,and P-selectin may be involved in the process of ne...Background：Acute kidney injury （AKI） is a severe disease in critically ill patients.Neutrophil infiltration into kidney was associated with the development of AKI,and P-selectin may be involved in the process of neutrophil recruitment in kidney.This study aimed to explore the potential effect of platelet-derived P-selectin on neutrophil recruitment in a mouse model of sepsis-induced AKI.Methods：A total of 30 C57BL/6 male mice were divided into five groups （n =6 in each）：sham group,sepsis group,anti-Ly6G group,anti-P-selectin group,and platelet depletion group.Sepsis was induced by cecal ligation and puncture.Serum creatinine concentration and platelet activity were measured by biochemical detector and flow cytometry,respectively.Histological and pathological features were analyzed using hematoxylin-eosin （HE） and immunohistochemi stry （IHC） staining,respectively.Myeloperoxidase （M PO） activity was detected with MPO assay.Unpaired t-test was used for data analysis.Results：Serum creatinine increased significantly in septic group compared to sham group （2.68 ± 0.27 mg/dl vs.0.82 ± 0.19 mg/dl,t =12.06,P =0.0000） but attenuated in antibodies-treated animals compared to septic group （anti-Ly6G：1.62 ± 0.30 mg/dl vs.2.68 ± 0.27 mg/dl,t =5.76,P=0.0004;anti-P-selectin：1.76 ± 0.31 mg/dl vs.2.68 ± 0.27 mg/dl,t =4.92,P =0.0012;and platelet depletion：1.93 ± 0.29 mg/dl vs.2.68 ± 0.27 mg/dl,t =4.14,P =0.0032）.Platelet amount significantly decreased compared to sham group （658.20 ± 60.64 × 109/L vs.822.00 ± 48.60 × 109/L,t =4.71,P =0.0015） in septic mice,especially in platelet depletion group （240.80 ± 44.98 × 109/L vs.822.00 ± 48.60 × 109/L,t =19.63,P =0.0000）.P-selectin activity was significantly increased in septic group compared to sham group （16.54 ± 1.60% vs.1.90 ± 0.29%,t =15.64,P =0.0000） but decreased significantly in platelet depletion group compared to septic group （3.62 ± 0.68% vs.16.54 ± 1.60%,t =12.89,P =0.0002）.IHC analysis shown that neutrophil infiltration increased in septic mice compared to sham group （36.67 ± 3.79% vs.9.17 ± 1.61%,t =11.58,P =0.0003） and function-blocked groups （anti-Ly6G：36.67 ± 3.79% vs.15.33 ± 1.53%,t =9.05,P 0.0008;anti-P-selectin：36.67 ± 3.79% vs.21.33 ± 1.53%,t =6.51,P=0.0029;and platelet depletion：36.67 ± 3.79% vs.23.33 ± 3.06%,t =4.75,P =0.0090）.MPO increased significantly in septic group compared to control （49.73 ± 1.83 ng/mg prot vs.13.04 ± 2.16 ng/mg prot,t =19.03,P =0.0000） but decreased in function-blocked groups compared to septic group （anti-Ly6G：26.52 ± 3.86 ng/mg prot vs.49.73 ± 1.83 ng/mg prot,t =9.59,P =0.0000;anti-P-selectin：33.06 ± 6.75 ng/mg prot vs.49.73 ± 1.83 ng/mg prot,t =4.85,P =0.0013;and platelet depletion：33.37 ± 2.25 ng/mg prot vs.49.73 ± 1.83 ng/mg prot,t =5.33,P =0.0007）.Conclusion：Platelets-derived P-selectin may be involved in the development of septic AKI through inducing neutrophil infiltration into kidney.展开更多
Selenocosmia huwena and Selenocosmia hainana are two tarantula species found in southern China.Their venoms contain abundant peptide toxins.Two new neurotoxic peptides,huwentoxin-Ⅲ(HWTX-Ⅲ) and hainantoxin-VI(HNTX-VI...Selenocosmia huwena and Selenocosmia hainana are two tarantula species found in southern China.Their venoms contain abundant peptide toxins.Two new neurotoxic peptides,huwentoxin-Ⅲ(HWTX-Ⅲ) and hainantoxin-VI(HNTX-VI),were obtained from the venom using ion-exchange chromatography and reverse-phase high performance liquid chromatography(RP-HPLC).The mechanism of action of HWTX-Ⅲ and HNTX-VI on insect neuronal voltage-gated sodium channels(VGSCs) was studied via whole-cell patch clamp techniques.In a fashion similar to δ-atracotoxins,HNTX-VI can induce a slowdown of current inactivation of the VGSC and reduction in the peak of Na+ current in cockroach dorsal unpaired median(DUM) neurons.Meanwhile,10 μmol/L HNTX-IV caused a positive shift of steady-state inactivation of sodium channel.HWTX-ⅡI inhibited VGSCs on DUM neurons(concentration of toxin at half-maximal inhibition(IC50)≈1.106 μmol/L) in a way much similar to tetrodotoxin(TTX).HWTX-Ⅲ had no effect on the kinetics of activation and inactivation.The shift in the steady-state inactivation curve was distinct from other depressant spider toxins.The diverse effect and the mechanism of action of the two insect toxins illustrate the diverse biological activities of spider toxins and provide a fresh theoretical foundation to design and develop novel insecticides.展开更多
基金This work was partly supported by grant from the Youth Fund of National Natural Science Foundation of China(81800441)Start-up Fund from Shanghai Fourth People’s Hospital Affiliated to Tongji University,Clinical Science and Technology Innovation Project of Shanghai Hospital Development Center,Construction and Application of Emergency and Critical Care Integrated Management Mode(SHDC22021211).
文摘Dear editor,Acute massive pulmonary embolism(PE) is a common life-threatening disease with high mortality of up to 30%–50%.[1,2]Potential heterogeneous reasons for PE remain controversial, and its treatment strategies mainly include antithrombotics, fibrinolytics, and embolectomy.
基金supported by grants from the Shanghai Health Bureau issues(2007102)
文摘BACKGROUND： Mechanical ventilation is a double-edged sword to acute respiratory distress syndrome （ARDS） including lung injury, and systemic inflammatory response high tidal volumes are thought to increase mortality. The objective of this study is to evaluate the effects of dynamic ventilatory factors on ventilator induced lung injury in a dog model of ARDS induced by hydrochloric acid instillation under volume controlled ventilation and to investigate the relationship between the dynamic factors and ventilator-induced lung injuries （VILI） and to explore its potential mechanisms.METHODS： Thirty-six healthy dogs were randomly divided into a control group and an experimental group. Subjects in the experimental group were then further divided into four groups by different inspiratory stages of flow. Two mL of alveolar fluid was aspirated for detection of IL-8 and TNF-α. Lung tissue specimens were also extracted for total RNA, IL-8 by western blot and observed under an electronic microscope.RESULTS： IL-8 protein expression was significantly higher in group B than in groups A and D. Although the IL-8 protein expression was decreased in group C compared with group B, the difference was not statistically significant. The TNF-a ray degree of group B was significantly higher than that in the other groups （P〈0.01）, especially in group C （P〉0.05）. The alveolar volume of subjects in group B was significantly smaller, and cavity infiltration and cell autolysis were marked with a significant thicker alveolar septa, disorder of interval structures, and blurring of collagenous and elastic fiber structures. A large number of necrotic debris tissue was observed in group B.CONCLUSION： Mechanical ventilation with a large tidal volume, a high inspiratory flow and a high ventilation frequency can cause significant damage to lung tissue structure. It can significantly increase the expression of TNF-α and IL-8 as well as their mRNA expression. Furthermore, the results of our study showed that small tidal ventilation significantly reduces the release of proinflammatory media. This finding suggests that greater deterioration in lung injury during ARDS is associated with high inspiratory flow and high ventilation rate.
基金Supported by The research grants from Shanghai Municipal Science and Technology CommissionNo.114119b2900+1 种基金Shanghai Municipal Key Laboratory of Pancreatic DiseaseNo.P2012006
文摘AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.8 folds vs 59.6±11.6 folds,P<0.01),ZO-1(46±18 folds vs68±19 folds,P<0.01),and E-cadherin proteins(48±15 folds vs 77±18 folds,P<0.01)were underexpressed in SAP intestinal epithelia although RhoA mRNA expression was not significantly changed in SAP(0.97±0.18 folds vs 1.01±0.17 folds,P>0.05).CONCLUSION:TNF-α-regulated miR-155 overexpression inhibits AJC component protein syntheses of ZO-1,and E-cadherin by downregulating post-transcriptional RhoA expression,and disrupts intestinal epithelial barrier in experimental SAP.
基金supported by the National Natural Science Foundation of China(grant number 81501654)Natural Science Foundation of Shanghai(grant number 14ZR1433700)
文摘BACKGROUND: Data on the mechanical ventilation(MV) characteristics and radiologic features for the cases with H7 N9-induced ARDS were still lacking.METHODS: We describe the MV characteristics and radiologic features of adult patients with ARDS due to microbiologically confirmed H7 N9 admitted to our ICU over a 3-month period.RESULTS: Eight patients(mean age 57.38±16.75; 5 male) were diagnosed with H7 N9 in the first quarter of 2014. All developed respiratory failure complicated by acute respiratory distress syndrome(ARDS), which required MV in ICU. The baseline APACHE II and SOFA score was 11.77±6.32 and 7.71±3.12. The overall CT scores of the patients was 247.68±34.28 and the range of CT scores was 196.3–294.7. The average MV days was 14.63±6.14, and 4 patients required additional rescue therapies for refractory hypoxemia. Despite these measures, 3 patients died.CONCLUSION: In H7 N9-infected patients with ARDS, low tidal volume strategy was the conventional mode. RM as one of rescue therapies to refractory hypoxemia in these patients with serious architectural distortion and high CT scores, which could cause further lung damage, may induce bad outcomes and requires serious consideration. Prone ventilation may improve mortality, and should be performed at the early stage of the disease, not as a rescue therapy.
基金supported by grants from National Natural Science Foundation(81272071)Techpool Foundation(01201111)
文摘BACKGROUND： Ulinastatin （UTI） is a urinary trypsin inhibitor extracted and purified from urine of males. This study aimed to explore the effects of UTI on paraquat-induced-oxidative stress in human type II alveolar epithelial cells. METHODS： The human type II alveolar epithelial cells, A549 cells, were cultured in vitro. The A549 cells were treated with different concentrations of paraquat （200, 400, 600, 800, 1 000, 1 200 pmol/L） and ulinastatin（0, 2 000, 4 000, 6 000, 8 000 U/mL） for 24 hours, the cell viability was measured by cell counting kit-8 and the median lethal concentration was selected. In order to establish an in vitro model of paraquat intoxication and to determine the safe dose of ulinastatin, we calculated LD50 using cell counting kit-8 to determine the survival rate of the cells. A549 cells were divided into normal control group, paraquat group and paraquat＋ulinastatin group. The levels of malondialdehyde （MDA） and myeloperoxidase （MPO） were detected by biochemistry colorimetry, while the level of reactive oxygen spies （ROS） was detected by DCFH-DA assay. RESULTS： The survival rate of A549 cells treated with different concentrations of paraquat decreased in a concentration-dependent manner. Whereas there was no decrease in the survival rate of cells treated with 0-4 000 U/mL ulinastatin. The levels of MDA, MPO, and ROS were significantly higher in the paraquat group than in the normal control group after 24-hour-exposure. And the survival rate of the paraquat＋ulinastatin group was higher than that of the paraquat group, but lower than that of the normal control group. The levels of MDA, MPO, and ROS were lower than those of the paraquat group. CONCLUSION： Ulinastatin can alleviate the paraquat-induced A549 cell damage by reducing oxidative stress.
基金the Wisdom Medical Research Project of Shanghai Municipal Health Commission(No.2018ZHYL0227)the Shanghai Science and Technology Commission(No.20DZ2200500).
文摘Introduction Human serum albumin(HSA)is a non-glycosylated,negatively charged,single-chain polypeptide composed of 585 amino acid residues with a relative molecular mass of 66.438 kD.It is synthesized by the liver at a rate of approximately 200 mg·kg^(-1)·day^(-1),with a half-life of 21 days,and subjected to catabolism in the muscles,liver,and kidneys at a rate of 4%per day.[1]Albumin,accounting for 60%of the total plasma protein,has various physiological functions,[2]such as maintaining 70%to 80%of effective plasma colloid osmotic pressure,coordinating vascular endothelial integrity,anti-oxidant and anti-inflammatory activities,maintaining the acidbase balance,and participating in the transport,distribution,and metabolism of a variety of endogenous and exogenous substances.
文摘Background：Acute kidney injury （AKI） is a severe disease in critically ill patients.Neutrophil infiltration into kidney was associated with the development of AKI,and P-selectin may be involved in the process of neutrophil recruitment in kidney.This study aimed to explore the potential effect of platelet-derived P-selectin on neutrophil recruitment in a mouse model of sepsis-induced AKI.Methods：A total of 30 C57BL/6 male mice were divided into five groups （n =6 in each）：sham group,sepsis group,anti-Ly6G group,anti-P-selectin group,and platelet depletion group.Sepsis was induced by cecal ligation and puncture.Serum creatinine concentration and platelet activity were measured by biochemical detector and flow cytometry,respectively.Histological and pathological features were analyzed using hematoxylin-eosin （HE） and immunohistochemi stry （IHC） staining,respectively.Myeloperoxidase （M PO） activity was detected with MPO assay.Unpaired t-test was used for data analysis.Results：Serum creatinine increased significantly in septic group compared to sham group （2.68 ± 0.27 mg/dl vs.0.82 ± 0.19 mg/dl,t =12.06,P =0.0000） but attenuated in antibodies-treated animals compared to septic group （anti-Ly6G：1.62 ± 0.30 mg/dl vs.2.68 ± 0.27 mg/dl,t =5.76,P=0.0004;anti-P-selectin：1.76 ± 0.31 mg/dl vs.2.68 ± 0.27 mg/dl,t =4.92,P =0.0012;and platelet depletion：1.93 ± 0.29 mg/dl vs.2.68 ± 0.27 mg/dl,t =4.14,P =0.0032）.Platelet amount significantly decreased compared to sham group （658.20 ± 60.64 × 109/L vs.822.00 ± 48.60 × 109/L,t =4.71,P =0.0015） in septic mice,especially in platelet depletion group （240.80 ± 44.98 × 109/L vs.822.00 ± 48.60 × 109/L,t =19.63,P =0.0000）.P-selectin activity was significantly increased in septic group compared to sham group （16.54 ± 1.60% vs.1.90 ± 0.29%,t =15.64,P =0.0000） but decreased significantly in platelet depletion group compared to septic group （3.62 ± 0.68% vs.16.54 ± 1.60%,t =12.89,P =0.0002）.IHC analysis shown that neutrophil infiltration increased in septic mice compared to sham group （36.67 ± 3.79% vs.9.17 ± 1.61%,t =11.58,P =0.0003） and function-blocked groups （anti-Ly6G：36.67 ± 3.79% vs.15.33 ± 1.53%,t =9.05,P 0.0008;anti-P-selectin：36.67 ± 3.79% vs.21.33 ± 1.53%,t =6.51,P=0.0029;and platelet depletion：36.67 ± 3.79% vs.23.33 ± 3.06%,t =4.75,P =0.0090）.MPO increased significantly in septic group compared to control （49.73 ± 1.83 ng/mg prot vs.13.04 ± 2.16 ng/mg prot,t =19.03,P =0.0000） but decreased in function-blocked groups compared to septic group （anti-Ly6G：26.52 ± 3.86 ng/mg prot vs.49.73 ± 1.83 ng/mg prot,t =9.59,P =0.0000;anti-P-selectin：33.06 ± 6.75 ng/mg prot vs.49.73 ± 1.83 ng/mg prot,t =4.85,P =0.0013;and platelet depletion：33.37 ± 2.25 ng/mg prot vs.49.73 ± 1.83 ng/mg prot,t =5.33,P =0.0007）.Conclusion：Platelets-derived P-selectin may be involved in the development of septic AKI through inducing neutrophil infiltration into kidney.
基金supported by the National Natural Science Foundation of China (No.30500146)the National Basic Research Program (973) of China (No.2006CB708508)
文摘Selenocosmia huwena and Selenocosmia hainana are two tarantula species found in southern China.Their venoms contain abundant peptide toxins.Two new neurotoxic peptides,huwentoxin-Ⅲ(HWTX-Ⅲ) and hainantoxin-VI(HNTX-VI),were obtained from the venom using ion-exchange chromatography and reverse-phase high performance liquid chromatography(RP-HPLC).The mechanism of action of HWTX-Ⅲ and HNTX-VI on insect neuronal voltage-gated sodium channels(VGSCs) was studied via whole-cell patch clamp techniques.In a fashion similar to δ-atracotoxins,HNTX-VI can induce a slowdown of current inactivation of the VGSC and reduction in the peak of Na+ current in cockroach dorsal unpaired median(DUM) neurons.Meanwhile,10 μmol/L HNTX-IV caused a positive shift of steady-state inactivation of sodium channel.HWTX-ⅡI inhibited VGSCs on DUM neurons(concentration of toxin at half-maximal inhibition(IC50)≈1.106 μmol/L) in a way much similar to tetrodotoxin(TTX).HWTX-Ⅲ had no effect on the kinetics of activation and inactivation.The shift in the steady-state inactivation curve was distinct from other depressant spider toxins.The diverse effect and the mechanism of action of the two insect toxins illustrate the diverse biological activities of spider toxins and provide a fresh theoretical foundation to design and develop novel insecticides.
