咪达普利与缬沙坦对兔动脉粥样硬化相关因子表达的影响及意义

Effects and significance of imidapril and valsartan on atherosclerotic related factors in rabbits

目的:研究咪达普利与缬沙坦对兔动脉中周期蛋白依赖激酶4(CDK4)、血管细胞黏附分子-1(VCAM-1)、信号转导及转录活化因子3(STAT3)和P15mRNA量的表达影响,探讨其抗动脉粥样硬化的机制。方法:48只雄性大白兔随机分为4组,对照组、高脂饮食组(高脂组)、高脂饮食加咪达普利组(咪达普利组)和高脂饮食加缬沙坦组(缬沙坦组)。喂养8周后处死兔子,测定各组血脂水平,并采用免疫组化法和RT-PCR法分别检测CDK4、VCAM-1、STAT3和P15mRNA量的表达。结果:高脂组、咪达普利组、缬沙坦组血清TC、TG、LDL-C水平均较对照组显著升高(均P<0.01)。咪达普利组和缬沙坦组内膜增生较高脂饮食组显著减轻(P<0.01)。CDK4、VCAM-1、STAT3在高脂组、咪达普利组和缬沙坦组中表达均较对照组显著增高(P<0.01);CDK4、VCAM-1、STAT3在咪达普利组和缬沙坦组中表达较高脂组显著减少(P<0.01)。P15mRNA表达在高脂组、咪达普利组和缬沙坦组均较对照组显著减少(P<0.01),在咪达普利组和缬沙坦组表达均较高脂组显著增高(P<0.01)。结论:咪达普利与缬沙坦可明显抑制动脉粥样硬化的发生,其机制与阻断STAT3信号转导通路、抑制内膜细胞增殖有关。

Objective：To investigate the effects of imidapril and valsartan on the expressions of cyclin-dependent kinase 4（CDK4）,vascular cell adhesion molecule-1（VCAM-1）,STAT3 and P15mRNA in rabbit aorta and the mechanism.Methods：Forty-eight rabbits were randomly divided into 4 groups：the control group,high cholesterol group,high cholesterol＋imidapril group and high cholesterol＋valsartan group.Artery blood samples were collected at the end of 8 weeks for examination of serum lipid levels.The expressions of CDK4,VCAM-1,STAT3 were detected by immunohistochemistry and the expressions of P15mRNA were detected by RT-PCR.Results：Rabbits fed with high-cholesterol diet showed higher serum lipid levels compared with those fed with normal diet（P0.01）.The intimal lesion in imidapril treated group and valsartan treated group reduced significantly than those of high cholesterol group（P0.01）.The expressions of CDK4,VCAM-1 and STAT3 in imidapril treated group and valsartan treated group decreased significantly than those of high cholesterol group（P0.01）,while the expressions of P15 mRNA of imidapril and valsartan group were higher than those of high cholesterol group（P0.01）.Conclusion：Imidapril,valsartan can inhibit atherosclerotic progression.The mechanism may be related to the inhibition of the proliferation of vascular smooth muscle cells in atherosclerosis.