瑞舒伐他汀对糖尿病合并冠心病大鼠动脉粥样硬化Rho激酶表达的影响

Effect of rosuvastatin on expression of Rho kinase in atherosclerosis of diabetes and coronary heart disease model rats

目的探讨瑞舒伐他汀对糖尿病合并冠心病大鼠动脉粥样硬化的防治作用及其相关机制。方法 Wistar大鼠50只,随机取10只大鼠以普通饮食喂养作为对照组,另40只以链脲佐菌素诱导糖尿病大鼠内膜损伤存活后,高脂饮食8周,取大鼠20只随机分为模型组、治疗组,每组10只,继续高脂饮食4周,之后治疗组用瑞舒伐他汀20mg/(kg·d)灌胃干预2个月。3组大鼠常规查血脂及RT-PCR检测主动脉血管细胞黏附分子1(VCAM-1)、细胞间黏附分子1(ICAM-1)及Rho激酶mRNA表达。结果干预前,与对照组比较,模型组和治疗组大鼠TC、TG、LDL-C水平显著升高,HDL-C水平显著降低(P<0.05)。干预后,与对照组比较,模型组大鼠TC、TG、LDL-C水平明显升高,HDL-C水平明显降低;VCAM-1、ICAM-1和Rho激酶mRNA表达增加,差异有统计学意义(P<0.01);与模型组比较,治疗组上述各指标均改善,差异有统计学意义(P<0.05,P<0.01)。结论瑞舒伐他汀通过干预 Rho/Rho激酶信号通路表达而抑制血管内皮炎症,起到延缓、抑制动脉管腔狭窄的作用,这可能为其抗动脉粥样硬化的新机制。

Objective To observe the inhibitory effect of rosuvastatin on atherosclerosis by Rho/ Rho kinase pathway in diabetes and coronary heart disease model rats,and to investigate its action mechanism. Methods Thirty Wistar rats were randomly divided into three groups：control group, atherosclerosis group,rosuvastatin group. The atherosclerosis group and rosuvastatin group were fed with high cholesterol diet for 12 weeks. After feeding drug for 2 months,vascular cell adhesion molecule-1（VCAM-1）, intercellular cell adhesion molecule-1 （ICAM-1） and Rho kinase mRNA were measured by reverse transcription polymerase chain reaction analysis. Results HE staining showed that atherosclerotic changes and changes of luminal structure in aorta of atherosclerosis group was increased as compared with the control group. Compared with atherosclerosis group, the expression of mRNA of VCAM-1, ICAM-1 and Rho kinase in rosuvastatin group was decreased （P 〈 0.05,P 〈 0.01）. Conclusions Rosuvastatin can inhibit early aortic inflammation and intima proliferation,thereby inhibiting the atheroselerotic plaque formation through Rho/Rho kinase signal transduction pathway.