肌球蛋白轻链激酶对早期实验性动脉粥样硬化兔动脉内皮功能的影响及机制探讨

动脉粥样硬化(AS)严重威胁人类健康，发病年龄趋于年轻化。早期AS以内膜增厚、弹力膜断裂、中层平滑肌细胞增生和迁移等病理变化为特征，且动脉内皮依赖性舒张功能（EDD）下降。我们先前研究表明在喂饲高胆固醇饮食1周时动脉壁（包括内膜、肌层）未出现明显结构变化，但肌球蛋白轻链激酶（MLCK）的表达和活性出现明显升高，并随胆固醇饮食喂饲时间的增加而增强，而MLCK表达和活性的升高可引起动脉肌层的收缩增强，MLCK抑制剂ML-7可明显增加实验性AS兔血管EDD。提示在高胆固醇血症和早期AS时，EDD降低可能与动脉壁MLCK表达和活性增加、收缩功能增强有关。本项目拟复制高胆固醇血症和AS兔模型，用高频超声检测EDD变化；动脉环离体实验检测内皮舒张功能；并观察高脂血清等对动脉内皮细胞舒张功能相关蛋白表达等影响，探讨实验性AS发生发展过程中兔动脉壁MLCK的表达及其活性的变化对EDD的影响及其调控机制。

Atherosclerosis (AS) threat to human health, tends to younger age of onset. Early AS is characterized by intimal thickening, elastic membrane rupture, medial smooth muscle cell proliferation and migration of pathological changes, and endothelial dependent diastolic function (EDD) decreased. our previous researchs demonstrated that when fed a high cholesterol diet for 1 weeks, there was no obvious change of structure in arterial intimal wall and muscle layer, but the myosin light chain kinase (MLCK) expression and activity increased significantly, and increase along with the cholesterol diet feeding time increase. The expression and activity of MLCK can cause arterial muscle contraction, MLCK inhibitor ML-7 can significantly increase the experimental AS rabbit vascular EDD. It is suggested that the decrease of EDD maybe related with increase of MLCK expression, activity and enhance of systolic function of arterial wall in hypercholesterolemia and early AS. This project aims to reproduce high cholesterol and AS rabbit model, to analyze the changes of EDD using high frequency ultrasound; to detect the endothelial function using artery ring analysis and to observe the expression of diastolic function related protein in arterial endothelial cells cultured with hyperlipemia serum, finally, to investigate the effect the expression and activity of rabbit arterial wall MLCK on EDD in development of early AS and its regulation mechanism.