吡格列酮对高脂血症大鼠主动脉凋亡蛋白Bax、Bcl-2的影响

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

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。

【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.