辛伐他汀对动脉粥样硬化时细胞外氧化/抗氧化系统作用及机制的实验研究

目的 :采用食饵性兔动脉粥样硬化 (AS)模型 ,探讨辛伐他汀对细胞外抗氧化的作用及其机制。方法 :雄性新西兰兔 4 2只 ( 1.983kg± 0 .182kg) ,随机分为正常对照组、AS组和辛伐他汀组。在实验前、造模第 8周和第 12周末分别测定血清胆固醇 (TC)、甘油三脂(TG)、超氧化物歧化酶 (SOD)、丙二醛 (MDA)及主动脉AS面积。结果 :随着喂饲高胆固醇 ,AS组血清TC、TG、MDA及主动脉AS面积逐渐升高 ,辛伐他汀组血清TC、TG、MDA及主动脉AS面积均显著低于同期AS组 (P <0 .0 1) ;AS组、辛伐他汀组SOD与正常对照组相比均无显著变化。结论 :辛伐他汀对AS形成中的细胞外内源性抗氧化酶活性并无影响 ,但其本身抗脂质过氧化作用是其抗AS作用的机制之一

The Effects of Simvastation on Lipid Peroxidation and Antioxidant Activity with Atherosclerosis rabbits induced by high cholesterol dietary

We sought to document the antioxidant mechanisms of t he antiatherogenic effects of the cholesterollowering hydroxy methylglutaryl co enzyme A(HMG CoA) reductase inhibitor simvastatin.Method: 42 rabbits were randomized into three groups.One group d id not receive treatments and served as normal control group,The second group we re fed regular chow with cholesterol and served as a atherosclerosis group.The t hird groups(simvastatin group) was fed the cholesterol enriched diet in conjun ction with simvastatin(Zocor) in a daily oral dose.The levels of serum total Ch olesterol and triglycerides were estimated at the baseline,the end of 8 and 12 w eeks after treatment,In order to evaluate the extracellular antioxidant status o f the rabbits,plasma malondialdehyde(MDA) and serum superoxide dismutase(SOD) we re measured as indexes of lipid peroxidation and antioxidant activity respective ly.The extent of aortic atherosclerosis was measured by planimetry of the sudano philic area.Results: The histopathological examination revealed marked alter ation in the aortic wall with the appearance of large multiple atheromatous plaq ues in atherosclerosis group and simvastatin group after treatment,The aortic wa ll atheroscleosis areas in simvastatin group is larger than atherosclerosis grou p at the same time( P<0.01 ).Also,the marked rise in serum cholesterol,serum t riglycerides that followed 12 weeks of cholesterol feeding was significantly red uced by simvastatin( P<0.05～0.01 ).The levels of serum SOD activity in all th ree groups were not changed during experiment( P>0.05 ).The levels of MDA in s imvastatin group and atherosclerosis group were rised significantly than that in normal control group( P<0.05～0.01 ),but the levels of MDA in simvastatin gro up were less significantly than that in atherosclerosis group( P<0.01 ).Conclusion: This study suggests that a reduction in lipid peroxi dation may be one of the antioxidant role of simvastatin itself,while it may not preserve or strengthen extracellular endogenous antioxidant activity directly.