吡格列酮对高脂血症大鼠主动脉血凝素样氧化型低密度脂蛋白受体1和凋亡蛋白表达的影响  

Effects of Pioglitazone on Expression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 and Apoptosis Protein in Aorta of Hyperlipidemia Rats

作　　者：李蓉[1,2] 蔡辉[1,2] 董晓蕾[1,2] 赵凌杰[1,2] 赵智明[1,2] 

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

出　　处：《中国动脉硬化杂志》2012年第7期600-604,共5页Chinese Journal of Arteriosclerosis

基　　金：中国博士后科学基金(20090461491)资助

摘　　要：目的观察吡格列酮对高脂血症大鼠主动脉血凝素样氧化型低密度脂蛋白受体1(LOX-1)和凋亡蛋白Bax、Bcl-2表达的影响,并探讨其作用机制及LOX-1在吡格列酮调节凋亡蛋白Bax、Bcl-2表达中的作用。方法清洁型SD大鼠26只,随机分为对照组(n=9)、高脂饮食组(n=17),高脂饮食组喂养12周后再随机分为模型组(n=8)和吡格列酮组(n=9),分别干预4周后,检测各组血脂水平,HE染色观察主动脉病理形态学改变,免疫组织化学法检测主动脉LOX-1、Bax和Bcl-2的表达。结果高脂饮食组喂养12周后,血脂明显升高(P<0.01);给药4周后,与模型组比较,吡格列酮组甘油三酯、总胆固醇水平明显降低(P<0.01),且主动脉血管内皮基本完好,偶有脱落,平滑肌细胞增殖不明显。与对照组相比,模型组主动脉LOX-1和Bax蛋白表达明显升高(P<0.01),Bcl-2蛋白表达和Bcl-2/Bax比值显著降低(P<0.01);与模型组相比,吡格列酮组主动脉LOX-1和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)。结论高脂饮食可引起主动脉LOX-1和凋亡蛋白Bax、Bcl-2及Bcl-2/Bax比值的改变,而吡格列酮可降低血脂,调节LOX-1和凋亡蛋白表达,抑制内皮细胞凋亡,从而改善内皮细胞功能和动脉粥样硬化病理进程。Aim To investigate effects of pioglitazone on the expression of lectin-like oxidized low-density lipoprotein receptor-1（LOX-1） and Bax,Bcl-2 in aorta of hyperlipidemia rats,and also to study the possible mechanism of pioglitazone,the effects of LOX-1 on pioglitazone regulating Bax,Bcl-2 expression.Methods 26 male SD rats were randomly divided into control group（n=9） and high-fat diets group（n=17）.High-fat diets group raised for 12 weeks were randomly divided into model group（n=8） and pioglitazone treated group（n=9）.After 4 weeks,serum lipid level of all rats was measured,HE staining was used to observe aortic pathological changes.LOX-1 and apoptosis protein of Bax,Bcl-2 in the aorta were analyzed by immunohistochemical method.Results After 12 weeks,the serum lipid level was significantly higher in high-fat diets group（P0.01）.Intervention with pioglitazone for 4 weeks,compared with modle group,serum levels of triglyceride（TG）,total cholesterol（TC） was decreased（P0.01）,and aortal endothelial tissue was intact,proliferation of smooth muscle cells were few in pioglitazone treated group.Compared with control group,the expression of LOX-1 and Bax protein in aorta were significantly increased（P0.01）,the Bcl-2 protein and ra-tio of Bcl-2/Bax was markedly decreased in model group（P0.01）.On the other hand,compared 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.Conclusions High-fat diets have an effect on expression of LOX-1 and apoptosis protein Bax and Bcl-2 in aorta,while pioglitazone can regulate the expression of LOX-1 and apoptosis protein,protecting endothelial from damage and apoptosis,improving the process of atherosclerotic pathological formation.

关 键 词：吡格列酮 高脂血症 血凝素样氧化型低密度脂蛋白受体1 BAX Bcl-2 动脉粥样硬化 

分 类 号：R5[医药卫生—内科学]