雷米普利对高胆固醇血症大鼠早期动脉粥样硬化的抑制作用

Inhibitory effect of ramipril on early atherogenesis in male rats with diet-induced hypercholesterolemia

目的探讨肾素血管紧张素系统(RAS)致早期动脉粥样硬化(AS)的机制。方法30只雄性SD大鼠分为正常对照(NC)组、高血脂(HL)组、雷米普利(Ram)组,每组10只。饲养10周后比色法测血清一氧化氮(NO)、丙二醛(MDA)水平及超氧化物歧化酶(SOD)活力,酶法测血胆固醇浓度;用免疫组化法检测主动脉血管壁增殖细胞核抗原(PCNA)和核转录因子(NFκB)及细胞间粘附分子1(ICAM 1)表达水平,HE染色高倍视野下计数浸润于内膜的单核细胞数。结果Ram组血清NO浓度和SOD活力显著高于HL组(P<0 01),而MDA水平低于HL组(P<0 01),NFκB活化、ICAM 1表达水平、血管壁PCNA阳性细胞数和浸润的单核细胞数明显低于HL组(P<0 01),但血胆固醇浓度3组间无差异。Ram组主动脉内皮损伤明显轻于HL组。结论雷米普利能缓解自由基损伤,抑制高胆固醇血症大鼠ICAM 1表达和单核细胞浸润,防止早期AS形成。

Objective To explore the mechanism that renin-angiotensin system(RAS) leads to early atherogenesis through observing the effects of ramipril on early atherogenesis in cholesterol-fed male rats.Methods Thirty male SD rats were divided into three groups:control group,hyperlipid group,and ramipril group.The rats were raised for ten weeks.Serum cholesterin,nitrous oxide(NO) and melondaldehyde(MDA) concentrations and superoxide dismutase(SOD) activity were measured.The aortas were collected for histopathlogical and immunohistochemical studies.Results Serum NO concentration and SOD activity increased significantly and serum MDA level decreased in rampril group compared with those in hyperlipide group(P<0.01).NFκB activation and ICAM-1 expression level,the number of the PCNA-positive cells and the monocytes infilitrating into the intima of the aortas in hyperlipide group was significantly higher than those in Ramipril groups(P<0.01).Serum cholesterin concentration of the above two groups showed no difference,but was significantly higher than that of control group.The endothelial damage of the aortas in Ramilpril groups was less severe than that in hyperlipide group.Conclusion Ramipril can prevent early atherogenesis through alleviating the damage to the arterial wall by free radicals,inhibiting the ICAM-1 expression and the monocytes infilitrating into the arterial wall.