瑞舒伐他汀与普罗布考抗大鼠动脉粥样硬化机制研究

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雄性大鼠,随机分5组,正常饮食组(A组),高脂饮食组(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周末处死各组大鼠,采血检测血脂,酶联免疫吸附法检测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)；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A组比较,B、C、D、E组大鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL-C)显著增高(P<0.01),高密度脂蛋白(HDL)降低(P<0.01),OX-LDL、VE-cadherin、MDA升高(P<0.01),而SOD降低(P<0.01),光镜下观察主动脉内膜厚度增加,内膜损害严重,动脉血管PECAM-1表达升高(P<0.01)。与B组比较,C、D、E组大鼠血清TC、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,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)。结论 普罗布考降低TC、LDL-C作用,以及抗炎效用与瑞舒伐他汀疗效相似,普罗布考有显著的抗氧化作用,抗氧化疗效优于瑞舒伐他汀,两药合用可减缓AS进展。

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

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.