瑞舒伐他汀与普罗布考抗大鼠动脉粥样硬化机制研究

Mechanism Research of Anti-atherosclerosis in Rats With Resuvastatin and Probucol

目的探讨选择性HMG-COA还原酶抑制剂瑞舒伐他汀(rosuvastatin)与抗氧化剂普罗布考(probucol)对大鼠动脉粥样硬化形成的影响,并研究其机制。方法 60只Wistar大鼠,♂,随机分正常饮食组(A组),模型组(B组),瑞舒伐他汀组(C组),普罗布考组(D组),瑞舒伐他汀联合普罗布考组(E组),每组12只。以高脂饲料喂养加腹腔注射VD3建立大鼠动脉粥样硬化(AS)模型。第9周,C、D、E组大鼠在高脂喂养基础上给予药物干预。16周末所有大鼠称重后处死,采血检测血脂、血浆氧化低密度脂蛋白(OX-LDL),血清丙二醛(MDA)、超氧化物歧化酶(SOD)、血管内皮细胞钙黏蛋白(VE-cadherin)水平;免疫组织化学法检测主动脉血小板内皮细胞黏附分子1(PECAM-1)的表达;光镜下观察主动脉血管壁病理组织学改变。结果与模型组(B组)比较,C、D、E组大鼠血清胆固醇(TC)、低密度脂蛋白(LDL-C)含量降低(P<0.01),OX-LDL、VE-cadherin、MDA明显下降(P<0.01),SOD升高(P<0.05),光镜下血管内膜较B组薄(P<0.01),内膜损害减轻,PECAM-1表达降低(P<0.01)。与C组比较,D组和E组OX-LDL、MDA降低(P<0.05),SOD升高(P<0.05)。光镜下观察,E组血管内膜厚度较C组、D组薄(P<0.05)。结论普罗布考降低TC、LDL-C浓度及抗炎作用与瑞舒伐他汀疗效相似,普罗布考抗氧化疗效优于瑞舒伐他汀,两药合用可使血管内膜的病理改变明显减轻,减缓AS的发展进程,提高对AS的治疗效果。

OBJECTIVE To discuss the effect of selective HMG-COA rosuvastatin and antioxidant probucol on atherosclerosis in rats, and research its mechanism. METHODS Sixty male Wistar rats were divided into control group（group A）, model group（group B）, rosuvastatin group（group C）, probucol group（group D）, and rosuvastatin combined probucol group（group E）, 12 rats in each group. High lipid-diet and intraperitoneal injection of Vitamin D3 were given to establish the atherosclerosis（AS） rat model. Group C, group D, and group E were intragastrically administered drug from the nineth week. All the rats were weighted and sacrificed for determination the levels of blood lipid, low-density lipoprotein（OX-LDL） in plasma, malonaldehyde（MDA）, superoxide dismutase（SOD）, vascular endothelial cadherin（VE-cadherin） in serum. The expression of platelet endothelial cell adhesion molecule-1（PECAM-1） was assayed by immunohistochemistry. The histomorphological changes of the aorta were observed under light microscope. RESULTS Compared with group B, the content of cholesterol（TC） and low-density lipoprotein（LDL） in group C, D and E were lower（P〈0.01）, the level of OX-LDL, VE-cadherin and MDA were significantly lower（P〈0.01）, the SOD activity increased（P〈0.05）, the intimal thickness was thinner（P〈0.01） and the endothelial damage of the aorta was lessened, and the expression of PECAM-1 was decreased（P〈0.01）. The levels of OX-LDL and MDA were lower and the SOD activity increased in group D and E than that in group C（P〈0.05）. The intimal thickness was thinner in group E than that in group C and D（P〈0.05）. CONCLUSION The therapeutic effects of probucol in reducing the level of TC, LDL is similar to rosuvastatin and the effect of antioxidation in probucol is superior to rosuvastatin. The two drugs combined together can decrease the histomorphological damage, slow the progress of AS, and improve treatment.