雷米普利和氯沙坦对高胆固醇血症大鼠早期动脉粥样硬化形成的影响

Inhibition of early atherogenesis by ramipril and losartan in male rats with diet-induced hypercholesterolemia

目的 :观察血管紧张素转换酶抑制剂 (ACEI)雷米普利和血管紧张素Ⅱ (AngⅡ ) 1型受体拮抗剂氯沙坦对高胆固醇血症大鼠早期动脉粥样硬化 (AS)形成的影响 ,探讨肾素 血管紧张素系统 (RAS)致早期AS的机制。方法 :4 0只雄性SD大鼠随机分为正常对照 (NC)组 ,高脂 (HL)组 ,雷米普利 (Ram )组和氯沙坦 (Los)组。每组 10只 ,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(I CAM 1)表达水平 ;透射电镜观察主动脉形态结构 ,苏木精 伊红染色高倍视野下计数浸润于内膜的单核细胞数。结果 :Ram组和Los组血清NO浓度和SOD活力显著高于HL组 (P <0 .0 1) ,而MDA水平低于HL组 (P <0 .0 1) ,NFκB活化及ICAM 1表达水平 ,PCNA阳性细胞数和浸润的单核细胞数明显少于HL组 (P <0 .0 1) ,但这三组间血胆固醇浓度差异无显著性意义。Ram组和Los组主动脉内皮损伤明显轻于HL组。结论 :Ram和Los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 and Losartan on early atherogenesis in cholesterol fed male rats. Methods:Forty male SD rats were randomly and equally divided into four groups: control group, hyperlipide group, Ramipril group and Losartan group. The rats were raised for ten weeks. Serum cholesterin, nitrous oxide (NO) and melondal dyhyde (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 and Losartan group as compared with those of 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 and Losartan groups (P< 0.01 ). Serum cholesterin concentration of the above three groups showed no difference, but were significantly higher than that of control group. The endothelial damage of the aortas in Ramilpril and Losartan groups was less severe than that in hyperlipide group. Conclusion:Ramipril and Losartan 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.