单硝酸异山梨酯对动脉粥样硬化兔血管内皮细胞功能的影响及机制探讨

摘要

目的 研究单硝酸异山梨酯对动脉粥样硬化兔血管内皮细胞功能的影响及机制. 方法 将30只新西兰大白兔随机分为对照组、高脂组、单硝酸异山梨酯组,每组10只.高脂组给予高胆固醇饲料(1.5%胆固醇+5%猪油的颗粒饲料)喂养,单硝酸异山梨酯组给予高胆固醇饲料+单硝酸异山梨酯0.5 g·kg-1·d-1.8周后,3%戊巴比妥(1 mL·kg-1)耳缘静脉注射麻醉,取兔腹主动脉做病理切片,行常规HE染色观察腹主动脉斑块的大小,行免疫组化染色检测植物血凝素样氧化低密度脂蛋白受体-1(LOX-1),P-选择素(P-selectin),并且应用全自动生化分析仪及血生化测定试剂盒,测定动脉硬化兔血清总胆固醇(TC)及三酰甘油(TG)的水平.结果 单硝酸异山梨酯组腹主动脉斑块的LOX-1和P-selectin的表达水平明显低于高脂组(P<0.05),但是血清TC、TG与高脂组间差异无统计学意义(P>0.05).结论 单硝酸异山梨酯具有延缓动脉粥样硬化进展的作用,其机制可能与下调LOX-1、P-selectin等黏附分子,减轻斑块炎性细胞浸润进而改善血管内皮细胞功能有关.%Objective To observe the therapeutic effects of Isosorbide Mononitrate on endothelial function in atherosclerosis in rabbits.Methods Thirty New Zealand white rabbits were randomly divided into three groups:control group,high cholesterol (1.5% Cholesterol+5% cocoa butter) group and Isosorbide Mononitrate (ISMN) group (high cholesterol diet + ISMN 0.5 g·kg-1·d-1,10 rabbits for each group.The extent of atherosclerotic plaque was evaluated by HE staining.The expression of LOX-1 and P-selectin was evaluated by immunohistochemistry staining.The serum total cholesterol (TC) and triglyceride (TG) were measured by a kit.Results The extent of atherosclerotic plaque was significantly lower in ISMN group than that of high cholesterol group.The expression of LOX-1 and P-selectin was lower in ISMN group than those of high cholesterol group.But there was no statistical difference of serum TC and TG level between ISMN group and high cholesterol group.Conclusion The results suggest that ISMN can alleviate the progress of AS by reducing the expression of adhesive molecule,inhibiting inflammatory response and improving endothelial function.