细胞凋亡和细胞自噬在慢性环孢素A肾毒性中的作用  

Role of apoptosis and autophagy in chronic cyclosporine A nephrotoxicity

作　　者：罗康[1] 朴尚国 金英顺[1] 邹洪斌[2] 苗里宁[3] 金华[1] 李灿[1] 

机构地区：[1]延边大学附属医院肾内科,吉林延吉133000 [2]吉林大学第一医院 [3]吉林大学第二医院

出　　处：《中国老年学杂志》2014年第11期3051-3053,共3页Chinese Journal of Gerontology

基　　金：国家自然科学基金资助项目(No.81160092)

摘　　要：目的探讨细胞凋亡和细胞自噬在慢性环孢素A(CsA)肾毒性中的作用。方法 Sprague-Dawley大鼠分为两组:对照组:皮下注射橄榄油(1 ml·kg-1·d-1)4 w;慢性CsA肾毒性组:皮下注射CsA(15 mg·kg-1·d-1)4 w。检测两组大鼠的体重和肾功能;三色染色检测肾小管间质纤维化程度;ELISA法检测血、尿8羟基脱氧鸟苷(8-OHdG)水平;原位末端标记法(TUNEL)染色观察细胞凋亡;免疫印迹法检测细胞凋亡调控基因(Bcl-2、Bax、Caspase-3)和细胞自噬体膜型LC3-Ⅱ蛋白的表达;Pearson直线相关分析肾小管间质纤维化程度与细胞凋亡和LC3-Ⅱ蛋白表达的相关关系。结果与对照组相比,毒性组大鼠体重减轻、肾功能低下、血尿8-OHdG水平升高,同时肾毒性组可见明显的肾小管间质纤维化和大量TUNEL阳性细胞。免疫印迹结果表明,毒性组Bax、Caspase-3、LC3-Ⅱ蛋白的表达明显增加,反之,Bcl-2的表达显著减少。直线相关分析提示,肾小管间质纤维化程度与TUNEL阳性细胞数和LC3-Ⅱ蛋白表达呈正向相关。结论细胞凋亡和细胞自噬参与了慢性CsA肾毒性肾小管间质的损伤。Objective To examine whether apoptosis and autophagy were involved in the pathogenesis of chronic cyclosporine A (CsA) nephrotoxicity.Methods Sprague-Dawley rats kept on a low salt diet (0.05%sodium) were treated daily for four weeks with subcu-taneous injections of vehicle (olive oil, 1 ml/kg) or CsA (15 mg/kg).Body weight and renal function were monitored .In addition, renal tubulointerstitial fibrosis , oxidative stress ( 8-OHdG ) , apoptotic cell death ( TUNEL assay ) , and expressions of apoptosis-related genes (Bcl-2, Bax, and Caspase-3) and LC3-Ⅱ (autophagy) were also measured.Results Compared with the normal treated rats, rats given CsA showed loss of body weight and renal dysfunction , with the development of striped tubulointerstitial fibrosis and increased TUNEL-posi-tive cells.CsA treatment significantly upregulated Bax , Caspase-3, and LC3-II expressions compared with those of vehicle group , whereas Bcl-2 protein expression was downregulated .These changes were accompanied by increase in serum and urinary 8-OHdG levels.Moreover, tubulointerstitial fibrosis was closely associated with the number of TUNEL-positive cells and LC3-II protein expression .Conclusions Apop-tosis and autophagy might be one of the molecular mechanisms in the tubulointerstitial fibrosis of chronic CsA nephrotoxicity .

关 键 词：慢性CsA肾毒性 细胞凋亡 细胞自噬 

分 类 号：R363.2[医药卫生—病理学]