伊贝沙坦对兔动脉粥样硬化的实验研究

目的　研究伊贝沙坦对兔氧化应激水平及其对动脉粥样硬化形成的影响。　方法　采用高胆固醇饲料喂饲另加牛血清白蛋白一次注射方法,建立家兔动脉粥样硬化模型。18只家兔分为正常对照组、模型组及伊贝沙坦组,每组各6只。8周后,取血清测血脂、丙二醛(MDA);取动脉行形态学检查及血管细胞黏附分子1(VCAM 1)的免疫组织化学染色。　结果　8周末模型组及伊贝沙坦组血脂水平高于正常对照组(P<0. 01),其中,伊贝沙坦组未对血脂产生影响,但血清MDA及主动脉内膜病变较模型组减少。免疫组织化学结果示伊贝沙坦组VCAM 1较模型组有显著下降(P<0. 05)。　结论　伊贝沙坦可有效抑制动脉粥样硬化的形成。该效应可能是通过抑制NAD(P)H氧化酶活性,并下调下游氧化还原敏感性基因的产物如VCAM 1而实现的。

Effect of irbesartan on formation of atherosclerosis in rabbits

Objective To investigate the experimental effect of irbesartan on oxidative stress and formation of atherosclerosis in rabbits. Methods An atherosclerotic rabbit model was established by feeding high cholesterol diet supplemented by bovine serum albumin injection. The rabbits were randomly divided into the control, model, and irbesartan treated group, six rabbits in each group. Blood samples were collected at the end of 8 weeks for examination of serum lipid levels and malondialdehyde(MDA) levels.The aortas were harvested for histomorphometric analysis , vascular cell adhesion molecule-1(VCAM-1) immunohistochemical analysis. Results The serum lipids levels of rabbits fed with high cholestrol diet higher than those of rabbits fed with normal diet (P<0.01). Treatment with irbesartan(10mg/kg per day) did not alter serum lipids levels. But the serum level of MDA and ratio of lesion of intimal area reduced significantly than those of model group (P< 0.05 ). The expression of VCAM-1 of the irbesartan treated group was decreased significantly than that of model group (P<0.05) . Conclusion Irbesartan can reduce the atherosclerotic progression by inhibiting the NAD(P)H oxidase activity and down-regulating the expression of redox sensitive genes in the downstream, such as VCAM-1.