【摘要】 目的：探究麝香通心滴丸(STDP)对缺血再灌注损伤的潜在保护作用及其改善冠状动脉微血管疾病(CMVD)内皮细胞功能的内在机制。方法：通过结扎和再灌注左冠状动脉前降支建立大鼠冠状动脉微血管疾病(CMVD)心肌缺血再灌注损伤模型。使用超声心动图、苏木精-伊红染色和伊文思蓝染色评估麝香通心滴丸(21.6毫克/千克)对心脏功能的影响。根据一氧化氮的产生量、内皮细胞一氧化氮合酶的表达、紧密连接(TJs)多样性结构和(ZO-1)、整合膜蛋白-5 (claudin-5)、闭合蛋白(occludin)和血管内皮钙黏蛋白(VE)-cadherin的表达评估麝香通心滴丸对微血管内皮屏障的影响。麝香通心滴丸(50和100纳克/毫升)的作用机制是通过检测1-磷酸鞘氨醇受体2 (S1PR2)、Ras同源家族成员A (Rho A)和Rho相关卷曲螺旋蛋白激酶(ROCK)的表达情况以及封闭小带-1(ZO-1)、血管内皮钙黏蛋白(VE)-cadherin和肌动蛋白(F-actin)在缺糖缺氧/复糖富氧模型中的分布情况来评估的。结果：麝香通心滴丸能明显改善冠状动脉微血管疾病大鼠模型心脏和微血管内皮细胞屏障功能(P <.05)。在体内，麝香通心滴丸(STDP)通过阐明和完善紧密连接(TJs)和提高封闭小带-1(ZO-1)、闭合蛋白(occludin)、整合膜蛋白-5 (claudin-5)和血管内皮钙黏蛋白(VE)-cadherin的表达来增强冠状动脉微血管定位和分布的结构完整性(P <0.05)。在体外，麝香通心滴丸通过抑制S1PR2/RhoA/ROCK通路来调节内皮细胞紧密连接(TJs)、粘附连接和细胞骨架形态。结论:麝香通心滴丸通过调节S1PR2/RhoA/ROCK通路，对心肌缺血再灌注损伤诱导的冠状动脉微血管疾病模型大鼠的心脏损伤和微血管内皮屏障损伤具有保护作用。更多还原

【Abstract】 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/m L) were evaluated by examining the expression of sphingosine 1-phosphate receptor 2(S1PR2),Ras Homolog family member A(Rho A),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/Rho A/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/Rho A/ROCK pathway.更多还原