补阳还五汤对动脉粥样硬化模型主动脉Rho激酶,PAl-1及eNOSmRNA表达的影响

目的:通过运用益气活血法的代表方剂补阳还五汤对动脉粥样硬化模型的干预,观察主动脉组织Rho激酶,纤溶酶原激活物抑制物-1(PAI-1)及内皮型一氧化氮合酶(e NOS)mRNA的表达、血脂等指标的变化,揭示该方药抗动脉粥样硬化作用的新靶点和新途径。方法:60只大鼠随机分为正常组,模型组,补阳还五汤低、高剂量组(10,20 g·kg-1),辛伐他汀组(0.6 mg·kg-1),补阳还五汤预防组(10 g·kg-1),除正常组外,其余各组维生素D3加高脂饮食诱导大鼠动脉粥样硬化模型,分别ig给予相应药物,补阳还五汤预防组给药的同时造模,造模成功后干预28 d,检测主动脉Rho激酶,PAl-1及e NOS mRNA表达,血脂水平总胆固醇(TC),甘油三酯(TG),高密度脂蛋白(HDL),低密度脂蛋白(LDL)和氧化型低密度脂蛋白(ox-LDL)。结果:与正常组比较,模型组大鼠Rho激酶,PAl-1 mRNA表达量水平明显升高,e NOS mRNA表达量水平明显降低及血脂TC,TG,LDL,ox-LDL水平明显升高(P0.01),HDL水平明显降低,均具有明显统计学差异(P0.01),补阳还五汤低、高剂量治疗组、辛伐他汀组、补阳还五汤预防组明显降低大鼠Rho激酶,PAl-1 mRNA表达量水平,明显升高e NOS mRNA表达量水平,明显降低血脂TC,TG,LDL,ox-LDL水平,明显升高HDL水平,均具有明显统计学差异(P0.05,P0.01)。结论:补阳还五汤可以下调Rho激酶,PAl-1 mRNA的表达,同时,上调e NOS mRNA的表达水平、降低血脂,具有抗动脉粥样硬化作用,抑制Rho激酶mRNA,PAl-1 mRNA表达及上调e NOS mRNA表达水平可能是其作用机制之一。

Effect of Buyang Huanwu Tang on Rho Kinase, PAl-1 and eNOS mRNA Expressions in Atherosclerosis Model Aorta

Objective: To study the effect of representative Qi-tonifying and blood-activating formulae Buyang Huanwu Tang (BYHWT) on the atherosclerosis model, in order to observe the aorta Rho kinase, PAl-1 and eNOS mRNA expressions and blood lipid indicator and reveal new targets and new ways of the formulae in inhibiting atherosclerosis. Method: Totally 60 rats were randomly divided into six groups:the normal control group, the model group, BYHWT low and high dose of groups (10, 20 g · kg^-1), the Simvastatin group (0.6 mg · kg^-1) and the BYHWT prevention group (10 g · kg^-1). Except for the normal group, the other groups were fed with VD₃ and high fat diet to induce atherosclerosis and given corresponding drugs. The BYHWT prevention group was administered with drugs during the modeling. After the successful modeling and 28-day intervention, the expression level of Rho kinase, plasma tissue plasminogen activator inhibitor 1(PAl-1), endothelial nitric oxide synthase(eNOS) mRNA expression, total cholesterol(TC), triglyceride(TG), high density lipoprotein cholesterin(HDL-C), low density lipoprotein cholesterin(LDL-C) and oxidized low-density lipoprotein(ox-LDL) in atherosclerosis aorta were detected. Result: Compared with the normal group, the model group showed significantly higher Rho kinase, PAl-1 mRNA expression, liquid TC, TG, HDL-C, ox-LDL and lower eNOS mRNA expression and LDL-C, all with significant statistical differences (P <0.01);BYHWT low and high dose groups, the Simvastatin group and the BYHWT prevention group showed notably lower Rho kinase, PAl-1 mRNA expression, lipid TC, TG, HDL-C, ox-LDL and higher eNOS mRNA expression, LDL-C, with significant statistical differences (P <0.05,P <0.01). Conclusion: BYHWT has an effect in down-regulating the Rho kinase and PAl-1 mRNA expression, up-regulating the eNOS mRNA expression and blood lipid, resisting atherosclerosis, inhibiting the Rho kinase and PAl-1 mRNA expression and increasing the Rho kinase and eNOS mRNA expression, which may be related to its mechanisms.