LOX-1在吡格列酮调节高脂血症大鼠主动脉凋亡蛋白表达中的作用  

Role of LOX-1 in Pioglitazone Regulating Apoptosis Protein in Aorta of Hyperlipidemia Rats

作　　者：李蓉[1] 蔡辉[2] 董晓蕾[2] 赵智明[2] 袁爱红[2] 

机构地区：[1]南方医科大学南京临床医学院,南京210002 [2]南京军区南京总医院,南京210002

出　　处：《微循环学杂志》2012年第2期17-20,100,I0001,共6页Chinese Journal of Microcirculation

基　　金：中国博士后科学基金资助项目(20090461491)

摘　　要：目的:观察吡格列酮对高脂血症大鼠主动脉血凝集素样氧化低密度脂蛋白受体-1(LOX-1)和凋亡蛋白Bax、Bcl-2表达的影响,探讨LOX-1在其中的变化和作用。方法:清洁级SD大鼠26只,随机分为正常组(n=9)、高脂饲料组(n=17),高脂饲料喂养12周后再随机分为高脂血症模型组(n=8)和吡格列酮组(n=9),分别给予生理盐水(正常组和模型组)和药物(吡格列酮组)干预4周后,常规方法检测各组血脂水平,免疫组织化学法检测各组主动脉LOX-1、Bax、Bcl-2蛋白表达,TUNEL染色法观察主动脉内膜细胞凋亡情况,并计算细胞凋亡指数(AI)。结果:高脂饲料喂养12周后,成功复制17只高脂血症模型大鼠。吡格列酮干预4周后,与模型组比较,吡格列酮组甘油三酯(TG)、胆固醇(TC)水平明显降低(P<0.01)。与正常组相比,模型组大鼠主动脉LOX-1、Bax蛋白表达明显增加(P<0.01),Bcl-2蛋白表达及Bcl-2/Bax比值明显降低(P<0.01);与模型组相比,吡格列酮组主动脉LOX-1、Bax蛋白表达明显降低(P<0.01),Bcl-2蛋白表达和Bcl-2/Bax比值明显升高(P<0.01),且吡格列酮组主动脉内膜AI亦较模型组显著降低(P<0.01)。结论:吡格列酮可改善高脂血症大鼠血脂水平,调节凋亡蛋白表达,减少主动脉内皮细胞凋亡,其作用可能与其下调LOX-1蛋白表达有关。Objective：To investigate influence of pioglitazone on the expression of LOX-1 and Bax,Bcl-2 on aorta in hyperlipidemia rats,and also to study the effects of LOX-1.Method：26 male SD rats were randomly divided into control group（n=9） and high-fat diets group（n=17）.High-fat diets rats raised for 12 weeks were randomly divided into model group（n=8） and pioglitazone treated group（n=9）,respectively gavaged with distilled water and pioglitazone.After 4 weeks,serum lipid level of all rats was measured.LOX-1 and apoptosis protein of Bax,Bcl-2 on the aorta were analyzed by immunohistochemical method.Terminal deoxynucleotidyl acyltransferase-mediated dUTP nick end labeling stained apoptotic cells in aortic intimal area to calculate apoptosis index.Results：After 12 weeks,17 rats raised with high-fat diets were successfully induced hyperlipidemia animal models.Intervention with pioglitazone for 4 weeks,compared with model group,serem levels of TG,TC were decreased（P0.01）.Compare with control group,the expression of LOX-1 and Bax protein on aorta were significantly increased（P0.01）,the Bcl-2 protein and ratio of Bcl-2/Bax was markedly decreased in model group（P0.01）.On the other hand,compare with model group,the expression of LOX-1 and Bax protein were lower,the Bcl-2 protein and ratio of Bcl-2/Bax were prominently higher in the pioglitazone treated group,moreover apoptotic index of aortic intima was significantly lower than the model group.Conclusion：Pioglitazone improves lipid levels in hyperlipidemia rats,which has an effect on expression of apoptosis protein Bax,Bcl-2 in aorta,reducing aortic endothelial cell apoptosis.This maybe have a relation to LOX-1 lowed.

关 键 词：吡格列酮 高脂血症 血凝集素样氧化低密度脂蛋白受体-1 内皮细胞凋亡 动脉粥样硬化 

分 类 号：R543.5[医药卫生—心血管疾病]