Ox-LDL诱导人肾小球系膜细胞凋亡在肾小球硬化中的作用  

Effect of mesangial cells apoptosis induced by Ox-LDL in glomerulosclerosis

作　　者：游天禄[1] 朱妙珍[2] 何娅妮[2] 

机构地区：[1]中国人民解放军第三军医大学第47医院,四川成都610500 [2]中国人民解放军第三军医大学大坪医院,重庆400042

出　　处：《现代中西医结合杂志》2003年第16期1697-1699,共3页Modern Journal of Integrated Traditional Chinese and Western Medicine

摘　　要：目的　探讨氧化低密度脂蛋白 (Ox -LDL)诱导肾小球系膜细胞凋亡的调控机制及其在肾小球硬化中的作用。方法　通过人肾小球系膜细胞体外培养 ,采用原位末端标记检测低浓度Ox -LDL对系膜细胞凋亡的影响 ,免疫组化法检测维生素E干预前后Ox -LDL对系膜细胞Bax/Bcl- 2表达的影响 ;按血浆LDL水平 ,把有不同程度肾小球硬化的慢性肾炎患者肾标本分为LDL正常组和LDL升高组 ,分别采用DNA原位末端标记和免疫组化法检测肾小球细胞凋亡及Bax/Bcl- 2蛋白表达。结果　低浓度Ox -LDL(<10 0mg/L)以剂量依赖方式促进肾小球系膜细胞凋亡 ,并使肾小球系膜细胞Bax的蛋白表达呈时间 -剂量依赖性增加 ,Bcl- 2的蛋白表达轻度升高后呈时间 -剂量依赖性下降 ,导致Bax/Bcl- 2比值增大 ;维生素E干预后这种变化不明显。LDL升高组肾小球细胞凋亡和Bax蛋白表达明显增加 ;Bcl- 2变化不明显 ,血LDL水平与肾小球硬化指数、凋亡指数、Bax/Bcl- 2比值有显著正相关关系。结论　Ox -LDL能诱导肾小球系膜细胞凋亡 ;Bax/Bcl- 2比值上升可能是Ox -LDL诱导肾小球系膜细胞凋亡的重要机制 ;Objective It is to investigate the mechanism of mesangial cell apoptosis induced by oxidized low density lipoprotein Ox LDL and its role in glomerulosclerosis. Methods Human renal mesangial cells were isolated and cultured in vitro. TUNEL technology was used to detect the apoptosis of mesangial cells induced by Ox LDL at low concentration. Immunohistochemistry technology was used to detect the effect of Ox LDL on expression of Bax/Bel 2 protein of mesangial cells before and after vitamin E intervention. Nephritic specimens of glomerulosclerosis patients were divided into normal LDL group and high LDL group according to serum LDL level. Apoptosis and Bax/Bcl 2 protein expression were detected with transferase mediated dUPT biotin nick end labeling (TUNEL) immunohistochemistry technology. Results Ox LDL accelerated mesangial cells apoptosis in dose dependent manner at low concentration (<100?mg/L). The Bax protein expression increased but the Bcl 2 protein expression decreased in dose and time dependent manner, which leaded to the ratio of Bax to Bcl 2 increase. Both Bax and Bcl 2 protein expression did not significantly increase after intervention with vitamin E. The apoptotic index and Bax protein expression of high LDL chronic nephritis patients were significantly higher than that of normal LDL chronic nephritis patients, but Bcl-2 protein expression did not significantly increase. The blood LDL level of chronic nephritis patients had a positive correlation with glomerulosclerosis, apoptotic index and the ratio of Bax to Bcl 2. Conclusion Ox LDL can induce mesangial cells apoptosis at low concentration. The increase of the ratio of Bax to Bcl 2 may be an important mechanism of cause of mesangial cells apoptosis induced by Ox LDL. Lipid abnormality may be an important cause of cell deletion leaded to glomerulosclerosis.

关 键 词：OX-LDL 人肾小球系膜 细胞凋亡 肾小球硬化 氧化低密度脂蛋白 

分 类 号：R692.6[医药卫生—泌尿科学]