大鼠阿霉素肾病肾小球细胞凋亡介导因子的表达及ACEI的影响

目的]探讨肾病肾小球细胞凋亡(脱噬作用)介导因子的表达及依那普利对其的影响。方法]8～10周雄性SD大鼠72只,随机分为干预组、模型组和对照组,各24只。于实验第1天、第21天分别对干预组、模型组大鼠注射阿霉素2mg/kg,对照组注射等量生理盐水。第2次注药后干预组大鼠的饮用水加入依那普利50mg/L。第2次注药后4周、12周、20周、28周各组分别处死4只大鼠,取肾组织行病理检测,并用末端标记法及电镜检测肾组织细胞凋亡。用免疫组化法检测肾组织Fas抗原(CD95)、Bcl-2蛋白和Ⅱ型血管紧张素Ⅱ受体(AT2R)表达;并计算其在肾小球中表达的阳性单位。结果]在20周后,干预组和模型组大鼠肾小球出现硬化,肾小球细胞调亡频率也显著增加。但干预组大鼠肾小球硬化指数(GSI)和肾小球细胞凋亡指数(GAI)均较模型组小。在20周和28周,干预组和模型组肾小球Fas抗原表达较对照组显著性增加,Bcl-2蛋白表达较对照组显著性降低;28周时,于预组肾小球Bcl-2蛋白表达较模型组显著性增高。3组大鼠肾组织AT2R的表达主要在远曲小管,肾小球中未见表达。在干预组和模型组,Fas抗原和Bcl-2蛋白阳性单位值与GSI和GAI相关均有显著性。结论]大鼠阿霉素肾病肾小球硬化时,肾小球细胞凋亡可能是受Fas抗原介导和Bcl-2蛋白调控的。依那普利于预可减少

The Expression of Apoptotic Mediators in Glomeruli in Adriamycin-induced Nephropathy in Rats and the Effect of ACEI

Objective] To detect the expression of apoptotic mediators in glomeruli in adri-amycin-induced nephropathy in rats and the effect of enalapril on it. Methods ] 72 male SD rats aged 8 - 10 weeks were randomly divided into three groups: intervention group (IG), model group (MG) and control group (CG) . Each group had 24 rats. Rats in IG and MG were given adriamycin (doxorubicin) 2 mg/kg intravenously on the 1st and the 21st day respectively. At the same time, an equal volume of normal saline was given to the rats in CG by the same method. After the second injection, rats in IG received enalapril(50 mg/L) in their drinking water. 4 rats in each group were killed every 8 weeks from the 4lh week after the second injection. Apoptotic cells in kidney samples were detected by TUNEL method and electron microscopy. The expression of Fas antigen (CD95), Bcl-2 protein and AT2R in kidney samples were detected by immunohistochemical staining respectively. Gray values of positive staining in glomeruli were obtained by computer image analyzer and quantified as positive unit (PU). Results] In IG and MG, glomerulosclerosis developed and the number of apoptotic cells in glomeruli increased after the 20th week. But glomerulosclerosis in IG was not so severer com- pared with that in MG at the 20th week. Glomerular cell apoptotic indexes (GAI) in IG at the 20th and 28th week were less than those in MG. The Fas antigen PUs in glomeruli were significantly increased and the Bcl-2 protein PUs in glomeruli were significantly decreased in IG and MG compared with CG at the 20th and 28th week. The Bcl-2 protein PUs in IG was significantly higher than that in MG at the 28th week. Expression of AT2R could not be detected in glomeruli. The PUs of Fas antigen and Bcl-2 protein in glomeruli in IG and MG were significantly correlated to glomerular sclerotic index (GSI) and GAI respectively. Conclusion] In the process of gromerulosclerosis in adriamycin-induced nephropa-thy, glomerular cell apoptosis may be induced by the increased expression of Fas antigen and the decreased expression of Bcl-2 protein. Enalapril intervention can partially reverse the reduction of Bcl-2 expression in glomeruli, which may contribute to reduce apoptosis during glomerulosclerosis in IG.