Objective:To investigate the potential protective effect of Shexiang Tongxin dropping pills(STDP)on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvas...Objective:To investigate the potential protective effect of Shexiang Tongxin dropping pills(STDP)on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease(CMVD).Methods:A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery.The effect of STDP(21.6 mg/kg)on cardiac function was evaluated using echocardiography,hematoxylin-eosin staining,and Evans blue staining.The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production,endothelial nitric oxide synthase expression,structural variety of tight junctions(TJs),and the expression of zonula occludens-1(ZO-1),claudin-5,occludin,and vascular endothelial(VE)-cadherin proteins.The mechanisms of STDP(50 and 100 ng/mL)were evaluated by examining the expression of sphingosine 1-phosphate receptor 2(S1PR2),Ras Homolog family member A(RhoA),and Rho-associated coiled-coil-containing protein kinase(ROCK)proteins and the distribution of ZO-1,VE-cadherin,and Factin proteins in an oxygen and glucose deprivation/reoxygenation model.Results:The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions(all P<.05).STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1,occludin,claudin-5,and VE-cadherin in vivo(all P<.05).The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro,leading to the regulation of endothelial cell TJs,adhesion junctions,and cytoskeletal morphology.Conclusion:STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.展开更多
目的:探讨开玄解毒方对于咪喹莫特诱导银屑病样小鼠模型的症状、体征改善及其对1-磷酸鞘氨醇(sphingosine-1-phosphate,S1P)水平的调节作用。方法:选用BALB/c小鼠25只,随机均分为正常组、模型组、甲氨蝶呤组、开玄解毒中剂量组和高剂量...目的:探讨开玄解毒方对于咪喹莫特诱导银屑病样小鼠模型的症状、体征改善及其对1-磷酸鞘氨醇(sphingosine-1-phosphate,S1P)水平的调节作用。方法:选用BALB/c小鼠25只,随机均分为正常组、模型组、甲氨蝶呤组、开玄解毒中剂量组和高剂量组,除正常组外,其余组采用外涂咪喹莫特法建立银屑病样皮损模型,连续干预7 d后取材。期间对皮损拍照并计算银屑病面积和严重程度指数(psoriasis area and severity index,PASI)评分;HE染色观察皮损病理改变及测量表皮厚度;对脾脏及胸腺拍照并称重;免疫组化法检测表皮Ki67、S1P表达;蛋白质印迹法检测皮损KRT17、Claudin、Occludin表达;qRT-PCR检测IL-17、IL-23、S1PRs mRNA表达水平。结果:与模型组比较,开玄解毒方可缓解咪喹莫特诱导的小鼠银屑病样皮损,降低PASI评分,减轻表皮增生程度(P均<0.01),改善胸腺、脾脏指数及血管增生情况(P<0.01或P<0.05),降低炎症因子IL-17、IL-23 mRNA表达(P<0.01),修复皮肤屏障(P<0.05)。同时,开玄解毒方可下调表皮中S1P及S1PRs mRNA表达(P<0.05)。结论:开玄解毒方能够减轻银屑病局部皮损症状,其药效机制可能与调节S1P水平有关。展开更多
基金supported the National Natural Science Foundation of China(81930113).
文摘Objective:To investigate the potential protective effect of Shexiang Tongxin dropping pills(STDP)on ischemia-reperfusion injury and its underlying mechanisms in improving endothelial cell function in coronary microvascular disease(CMVD).Methods:A rat model of myocardial ischemia-reperfusion injury with CMVD was established using ligation and reperfusion of the left anterior descending artery.The effect of STDP(21.6 mg/kg)on cardiac function was evaluated using echocardiography,hematoxylin-eosin staining,and Evans blue staining.The effects of STDP on the microvascular endothelial barrier were assessed based on nitric oxide production,endothelial nitric oxide synthase expression,structural variety of tight junctions(TJs),and the expression of zonula occludens-1(ZO-1),claudin-5,occludin,and vascular endothelial(VE)-cadherin proteins.The mechanisms of STDP(50 and 100 ng/mL)were evaluated by examining the expression of sphingosine 1-phosphate receptor 2(S1PR2),Ras Homolog family member A(RhoA),and Rho-associated coiled-coil-containing protein kinase(ROCK)proteins and the distribution of ZO-1,VE-cadherin,and Factin proteins in an oxygen and glucose deprivation/reoxygenation model.Results:The administration of STDP on CMVD rat model significantly improved cardiac and microvascular endothelial cell barrier functions(all P<.05).STDP enhanced the structural integrity of coronary microvascular positioning and distribution by clarifying and completing TJs and increasing the expression of ZO-1,occludin,claudin-5,and VE-cadherin in vivo(all P<.05).The S1PR2/RhoA/ROCK pathway was inhibited by STDP in vitro,leading to the regulation of endothelial cell TJs,adhesion junctions,and cytoskeletal morphology.Conclusion:STDP showed protective effects on cardiac impairment and microvascular endothelial barrier injury in CMVD model rats induced by myocardial ischemia-reperfusion injury through the modulation of the S1PR2/RhoA/ROCK pathway.
文摘目的:探讨开玄解毒方对于咪喹莫特诱导银屑病样小鼠模型的症状、体征改善及其对1-磷酸鞘氨醇(sphingosine-1-phosphate,S1P)水平的调节作用。方法:选用BALB/c小鼠25只,随机均分为正常组、模型组、甲氨蝶呤组、开玄解毒中剂量组和高剂量组,除正常组外,其余组采用外涂咪喹莫特法建立银屑病样皮损模型,连续干预7 d后取材。期间对皮损拍照并计算银屑病面积和严重程度指数(psoriasis area and severity index,PASI)评分;HE染色观察皮损病理改变及测量表皮厚度;对脾脏及胸腺拍照并称重;免疫组化法检测表皮Ki67、S1P表达;蛋白质印迹法检测皮损KRT17、Claudin、Occludin表达;qRT-PCR检测IL-17、IL-23、S1PRs mRNA表达水平。结果:与模型组比较,开玄解毒方可缓解咪喹莫特诱导的小鼠银屑病样皮损,降低PASI评分,减轻表皮增生程度(P均<0.01),改善胸腺、脾脏指数及血管增生情况(P<0.01或P<0.05),降低炎症因子IL-17、IL-23 mRNA表达(P<0.01),修复皮肤屏障(P<0.05)。同时,开玄解毒方可下调表皮中S1P及S1PRs mRNA表达(P<0.05)。结论:开玄解毒方能够减轻银屑病局部皮损症状,其药效机制可能与调节S1P水平有关。
