辛伐他汀减轻载脂蛋白E^(-/-)小鼠氧化应激及小窝蛋白1的表达  

Effects of Simvastatin on Early Oxidative Stress and Caveolin-1 in Apolipoprotein E-Deficient Mice

作　　者：尹冬华[1] 桂鸣[1] 刘猛[1] 黄峻[1] 

机构地区：[1]南京医科大学第一附属医院心脏科,江苏南京210029

出　　处：《中华高血压杂志》2008年第8期700-703,共4页Chinese Journal of Hypertension

基　　金：江苏省教育厅自然科学基金(01KJB320003);南京医科大学创新基金(CX003001)

摘　　要：背景氧化应激损伤内皮是动脉粥样硬化的始动因素,他汀对于动脉粥样硬化的干预主要集中在粥样硬化斑块形成之后,而对于粥样硬化斑块形成之前的研究较少。目的观察辛伐他汀对载脂蛋白(apo)E^(-/-)小鼠氧化应激及主动脉内皮小窝蛋白l的影响,探讨辛伐他汀在动脉粥样硬化一级预防中保护内皮功能的机制。方法24只6周龄雄性 apoE^(-/-)小鼠,随机等分为两组:对照组、辛伐他汀[5 mg/(kg·d)]治疗组,4周后处死动物。常规生物化学法测定血总胆固醇(TC)、超氧化物歧化酶活性(SOD)、丙二醛(MDA)和血清一氧化氮(N0)含量。采用苏木素伊红(HE)染色法观察小鼠主动脉内皮组织,免疫组织化学法分析小鼠主动脉内皮的小窝蛋白1的表达。结果两组间血脂水平无显著性差异。辛伐他汀治疗组主动脉内皮组织的损伤减轻(损伤阳性率33.3%比对照组:75%,P<0.05)。治疗4周后,辛伐他汀治疗组 SOD[(135.3±5.5)U/L 比对照组:(97.2±7.6)U/L,P<0.01)和 NO[(28.4±4.1)μmol/L 比对照组:(12.3±2.1)μmol/L,P<0.01]均明显升高,MDA 显著减低[(10.5±0.5)nmol/L 比对照组:(17.3±1.0)nmol/L,P<0.01]。辛伐他汀治疗组主动脉内皮上小窝蛋白1的表达(表达阳性率41.67%比对照组:83.33%,P<0.05)明显降低。结论辛伐他汀在不影响血脂水平情况下,抑制主动脉内皮的小窝蛋白1的表达,减轻 apoE^(-/-)小鼠氧化应激,增加 NO 水平,起到改善内皮功能、抗动脉粥样硬化作用,在动脉粥样硬化的一级预防中可能发挥重要作用。Background Rare studies on the effect of statin on early stage of atherosclerosis have been reported. Oxidative stress induced endothelial dysfunction may be the initiative factor for the development of atherosclerotie plague. Objective To investigate the mechanisms by which simvastatin, prevents atherosclerosis independently of its lipid-lowering effect in Apolipoprotein E-deficient mice. Methods Twenty-four 6-week old male apoE- deficient mice were randomly to receive placebo or simvastatin 5 mg/（kg · d） by gavage for 4 weeks. Total cholesterol （TC）, super-oxide dismutase （SOD）, malondialdehyde （MDA） and serum nitric oxide （NO） were measured by biochemical analysis. Endothelium was observed by HE dyeing. The expression of caveolin-1 in aortic wall was detected by immunohistochemistry. Results There was no significant difference in serum TC between control and simvastatin treatment groups. Simvastatin caused less damaged endothelium（33.33% vs control＇s： 75%, P〈 0. 05） than control group. Compared with the control＇s, simvastatin significantly decreased serum MDA level（10. 5 ±0. 5 nmol/L vs control＇s： 17.3± 1.0 nmol/L, P〈0. 01 ）, increased serum SOD level （ 135. 3 ± 5.5 U/L vs controls. 97.2±7. 6 U/L, P〈0.01） and NO level （28. 4±4. 1 umol/L vs control＇s： 12. 3±2. 1 umol/L, P〈0.01） at 4 weeks. Expression of caveolin-1 was significantly inhibited by simvastatin treatment （ 41.67% vs control＇s： 83. 33%, P〈0. 05 ） . Conclusion The effects that simvastatin attenuates oxidative stress and protects endothelial function were associated with downregulating of caveolin-1 expression in aortic wall, decreasing serum MDA level, increasing serum SOD level and NO level, and were independent from its cholesterol-lowering effect.

关 键 词：辛伐他汀 载脂蛋白E^-/-小鼠 氧化应激 小窝蛋白1 

分 类 号：R543[医药卫生—心血管疾病]