吡格列酮对高脂血症大鼠主动脉凋亡蛋白Bax、Bcl-2的影响

目的探讨吡格列酮对高脂血症大鼠主动脉凋亡蛋白Bax、Bcl-2表达的影响及保护血管内皮的可能机制。方法清洁型SD大鼠26只,随机分为对照组(n=9)和高脂饮食组(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,检测各组血脂水平和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Bax、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TG、TC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Bax蛋白表达明显增高(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凋亡蛋白Bax、Bcl-2及比值的改变,而吡格列酮可降低血脂,调节Bax、Bcl-2凋亡蛋白表达,抑制内皮细胞凋亡,改善内皮细胞功能和动脉粥样硬化病理进程。

Influence of Pioglitazone on Bax & Bcl-2 protein expression of aorta in hyperlipidemia rats

【Objective】 To investigate the change of apoptosis protein of Bax & Bcl-2 on aorta in hyperlipidemia rats treated with Pioglitazone,and also to study the possible mechanism of Pioglitazone improved endothelium cell.【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 and apoptosis protein of Bax & Bcl-2 on the aorta was analyzed by immunohistochemical method,while using HE staining to observe aortic pathological changes.【Results】 High-fat diets group was raised for 12 weeks,the serum lipid level was significantly higher(P <0.01).Intervention with Pioglitazone for 4 weeks,compared with the model group,serem levels of TG,TC was decreased(P <0.01),and aortal endothelial tissue was completed primitively,proliferation of smooth muscle cells were not obviously.To contrast with control group,the expression of Bax protein on aorta was significantly increased(P <0.01),the Bcl-2 protein and ratio of Bcl-2/Bax was markedly decreased in model group(P <0.01).At the same time,the expression of Bax protein was lower and the Bcl-2 protein and ratio of Bcl-2/Bax was prominently higher in the Pioglitazone treated group than model group.【Conclusions】 High-fat diets have an effect on expression of apoptosis protein Bax & Bcl-2 in aorta,in contrast Pioglitazone can regulate the expression of apoptosis protein Bax & Bcl-2 and the ratio of Bcl-2/Bax,protecting endothelial from damage and apoptosis,to improve the process of atherosclerotic pathological formation.