普罗布考对动脉粥样硬化兔血红素氧合酶1表达的影响

Effect of Probucol on Heme Oxygenase-1 in Rabbits with Atherosclerosis

目的观察血红素氧合酶1蛋白在兔主动脉粥样硬化病变和肝脏中的表达以及普罗布考对血红素氧合酶1表达的影响。方法16只新西兰大白兔建立动脉粥样硬化模型后,随机加喂普罗布考(n=8,普罗布考组)或淀粉(n=8,淀粉组)6周。观察两组兔以及正常新西兰大白兔(n=8,正常对照组)血脂、体重和血清丙二醛含量。采用免疫组织化学法测定主动脉和肝脏血红素氧合酶1蛋白的表达。结果与淀粉组相比,普罗布考组血红素氧合酶1在主动脉和肝脏内表达增多,动脉粥样斑块减少,血清总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和丙二醛明显降低。血红素氧合酶1在动脉内膜斑块、动脉平滑肌以及肝脏内的表达水平与血清丙二醛、主动脉斑块面积、内膜厚度、动脉内膜中膜厚度比均呈明显负相关(P均<0.05)。结论普罗布考在降低胆固醇的同时,还可能通过上调血红素氧合酶1发挥抗氧化作用,这可能是其抗动脉粥样硬化的重要途径。

Aim To observe the effect of probucol on the expression of heme oxygenase- 1 { HO- 1 ） protein in athoroselerotic lesions and livers in rabbits. Methods The hypercholestrolemic model was built up by 8 weeks high cholesterol diet. Then 16 New Zealand rabbits were randomly fed with starch （ n = 8, starch group） or probucol （n = 8, probucol group ） for 6 weeks. Those two groups and another 8 New Zealand rabbits （n = 8, control group） were tested for serum lipid, body weight and serum malon dialdehyde （MDA）. Expression of HO-1 was detected by immunohistochemistry. Results Probucol treatment increased HO-1 expression in atherosclemtic plaque, aorta smooth muscle cell and liver, decreased atherosclemtic areas, initma thicknesses, and ratio of intimae to media, and down regulated serum total cholesterol （TC）, low density lipoprotein cholesterol （ LDLC）, high density lipoprotein cholesterol （HDLC） and MDA. Expression of HO-1 protein in atherosclerotic plaque, smooth muscle cell and liver in hypercholesterolemic rabbits with and without probucol treatment was negatively correlated with serum levels of MDA, atherosclerotic areas,imimae thickness,and the ratio of infimae to media （ P 〈 0.05）. Conclusions While lowering serum cholesterol, probucol may also exert anti-oxidative actions through upregulation of HO-1 expressions, which might be an important part of its anti-atherogenic properties.