通心络减轻糖尿病心肌缺血/再灌注损伤与其改善内皮屏障功能有关

Protection of Tongxinluo Against Myocardial Ischemia/Reperfusion Injury Relates to Enhancing Endothelial Barrier in Diabetic Rats

目的:探讨通心络对糖尿病心肌缺血/再灌注损伤的影响是否与调控内皮屏障功能有关。方法:将32只Zucker糖尿病大鼠随机分为假手术组,模型组,胰岛素组,通心络组,每组8只。8只Zucker非糖尿病大鼠作为对照组。通过进行心肌缺血45 min/再灌注3 h干预以建立心肌再灌注损伤模型。通过病理染色法测定心肌梗死面积。采用Miles法,通过酶标仪测定心肌组织萃取液异硫氰酸荧光素浓度,从而反映心肌微血管通透性。利用膜蛋白提取和蛋白印迹(Western blot)技术检测聚乙二醇辛基苯基醚(Triton X-100)不溶性和可溶性血管内皮钙黏蛋白的表达量。结果:模型组梗死面积显著高于对照组[(55.2±1.4)%vs(36.2±1.3)%,P<0.05],模型组异硫氰酸荧光素浓度和血管内皮钙黏蛋白内化显著高于对照组。胰岛素组和通心络组梗死面积均低于模型组[(36.8±1.2)%vs(38.7±1.1)%,P>0.05],胰岛素组和通心络组异硫氰酸荧光素浓度(P<0.01)和血管内皮钙黏蛋白内化(P<0.05)均明显低于模型组。结论:通心络减轻心肌缺血/再灌注损伤与保护内皮屏障功能有关,这一保护作用不依赖于降糖治疗,并且不亚于胰岛素降糖治疗。

Objective： To clarify that protection of Tongxinluo against myocardial ischemia/reperfusion injury relates to enhancing endothelial barrier in diabetic rats.Methods： A total of 32 Zucker diabetic rats were randomized into 4 groups： Sham group, Model group, Insulin group and Tongxinluo group, n=8 in each group. In addition, there was a Control group containing 8 non-diabetic Zucker rats. Myocardial ischemia/reperfusion injury model was established by a 45-min ischemia and 3-h reperfusion protocol. The size of infarction was detected by pathological staining, the microvascular permeability was examined by Miles assay to obtain the fluorescein isothiocyanate concentration in myocardial tissue, the Triton X-100 soluble and insoluble VE-cadherin was measured by membrane protein extraction and western blot analysis.Results： The size of infarction in Model group was obviously higher than that in Control group（55.2 ± 1.4） % vs（36.2± 1.3） %, P0.05 and the fluorescein isothiocyanate concentration was also higher in Model group than Control group. Both insulin group and Tongxinluo group had the similar size of infarction with Model group（36.8 ± 1.2） % vs（38.7 ± 1.1） %, P0.05. Both insulin group and Tongxinluo group got lower fluorescein isothiocyanate concentration（all P0.01） and VE-cadherin internalization（all P0.05） than that in Model group.Conclusion： Protection of Tongxinluo against myocardial ischemia/reperfusion injury in diabetic rats is as effective asinsulin, but the effect is independent of reducing blood glucose and may be related to enhancing endothelial barrier.