辛伐他汀通过Rho/Rho激酶信号通路抑制高血压模型大鼠的心血管重构研究

Inhibitory Effects of Simvastatin on Cardiovascular Remodeling of Hypertensive Model Rats by Rho/Rho Kinase Signal Pathway

目的:研究辛伐他汀抑制高血压模型大鼠心血管重构的作用及其机制。方法:将60只大鼠均分为模型组和阴性对照组,模型组大鼠连续给药3周建立高血压模型,检测2组大鼠血压、主动脉结构变化和Rho激酶mRNA及其A蛋白的表达。然后将模型组大鼠分为低、中、高剂量(0.1、1、10mg/kg)辛伐他汀组(n=9),阴性对照组中选取9只大鼠作为对照组,每日灌胃相应药物1次,8周后处死大鼠,检测4组大鼠主动脉结构变化和Rho激酶mRNA及其A蛋白的表达。结果:与阴性对照组比较,模型组大鼠收缩压、舒张压、Rho激酶mRNA及其A蛋白表达均明显增加(P<0.01),主动脉内膜明显增生,内膜厚度增宽,表明高血压模型建模成功。与对照组比较,低、中、高剂量辛伐他汀组大鼠主动脉内膜增生程度、Rho激酶mRNA及其A蛋白表达均明显降低(P<0.05),且均呈剂量依赖性。结论:辛伐他汀可能通过Rho/Rho激酶信号通路抑制高血压模型大鼠的心血管重构。

OBJECTIVE： To study the inhibitory effects of simvastatin on cardiovascular remodeling of hypertensive model rats and its mechanism. METHODS： 60 rats were randomly divided into model group and negative control group. Hypertensive model was established for rats continuously for 3 weeks in model group, the changes of blood pressure and aortic structure were detected and mRNA and protein expression of RhoA were determined. And then model group were divided into simvastatin low-dose, medi- um-dose and high-dose groups （0.1, 1, 10 mg/kg） （n=9） ; 9 rats in negative control group were included in control group. They were given relevant medicine once a day, and 8 weeks later they were scarificed. The changes of aortic structure, mRNA and pro- tein expression of RhoA were determined in 4 groups. RESULTS： Compared with negative control group, systolic blood pressure, diastolic blood pressure, mRNA and protein expression of RhoA were increased significantly in model group （P〈0.01）, and hyper- tensive model was established successfully through aortic intimal hyperplasia and intimal thickness broadening. Compared with con- trol group, aortic intimal hyperplasia, mRNA and protein expression of RhoA were decreased significantly in low-dose, medi- um-dose and high-dose groups （P〈0.05）, in dose-dependant manner, CONCLUSIONS： Simvastatin can inhibit the cardiovascular remodeling of hypertensive rats by Rho/Rho kinase signal pathway.