缬沙坦抗氧化应激及其对动脉粥样硬化的实验研究

目的 :研究缬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、模型组及缬沙坦组 ,各组 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粘附分子 1(VCAM 1)的免疫组织化学染色 ;并用超氧化物荧光探针DHE检测原位超氧化物以反映NAD(P)H氧化酶的活性。结果 :8周末 ,模型组及缬沙坦组血脂水平高于正常对照组 (P <0 .0 1) ,其中 ,缬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缬沙坦组VCAM 1较模型组有显著下降 (P <0 .0 5 ) ;另外 ,血管原位超氧化物也明显下降。结论 :缬沙坦可有效抑制动脉粥样硬化的形成 ,且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产生而实现的

Experimental Studies of Valsartan on Oxidative Stress and the Formation of Atherosclerosis

Objective: To investigate the experimental effect of valsartan on oxidative stress and the formation of atherosclerosis in rabbit.Method: An atherosclerotic rabbit model was established by feeding high cholesterol diet supplemented by bovine serum albumin injection bolus. The rabbits were randomly divided into the control, model, and valsartan treated group,six rabbits in each group. Blood samples were collected at the end of 8 weeks for examination of serum lipid levels and MDA levels; the aortas were harvested for histomorphometry analysis, vascular cell adhesion molecule-1(VCAM-1) immunohistochemistry analysis and in situ superoxide detection to reflect the activity of NAD(P)H oxidase.Results: Rabbits fed with high cholestrol diet showed higher serum lipids levels than those fed with normal diet(P<0.01). Treatment with valsartan(10 mg/kg per day) did not alter serum lipids levels. But the serum MDA level and ratio of lesion to intimal area reduced significantly compared witi model group(P<0.05). The expression of VCAM-1 decreased significantly in the valsartan treated group than in the model group(P<0.05).In addition, in situ superoxide detection also show the markedly reduction of superoxide as a result of valsartan treatment.Conclusion: These results indicate that the valsartan treatment can reduce the atherosclerotic progression by inhibiting the NAD(P)H oxidase activity to produce superoxide and downregulating the expression of redox sensitive genes in the downstream, such as VCAM-1.