The significance of expression of Fas antigen and Bcl-2 protein in the kidney of adriamycin induced nephrosis in rats

Sun Liangzhong, Yue ZH, Xu HS, Chen SM, Liang M, Tang JR

Department of Pediatrics, The First Affiliated Hospital,

Sun Yat-Sen University of Medical Sciences, Guangzhou, China

Subject: To further understanding the mechanism of apoptosis in the process of glomerulosclerosis.

Methods: 72 male SD rats aged 8~10 weeks were randomly divided into three groups (A, B, C), each group had 24 rats. Rats in group A and B were given adriamycin 2mg/kg intravenously on the 1st and the 21st day respectively. At the same time, an equal volume of natural solution was given to the rats in the group C by the same method. After the second injection, rats in group A received enalapril (50mg/L) in their drinking water. 4 rats in each group were killed every 8 weeks from the 4th week after the second injection. Apoptotic cells in the kidney samples were detected by in the TUNEL method and the electronic microscopy. The expression of Fas antigen, 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 group A and B, glomerulosclerosis was emerged and the number of apoptotic cells in glomeruli increased after the 20th week. But glomerulosclerosis in the group A was not so severer compared with that in the group B at the 20th week. Glomerular cell apoptotic index (GAI) in group A at the 20th and 28th week were less than those in group B. The expression Fas antigen was significantly increased and the expression of Bcl-2 protein was significantly decreased in glomeruli in group A and B after the 20th week. The differences of Fas antigen expression in glomeruli between group A and B had not significant. But the expression of Bcl-2 protein in glomeruli was partially reserved in group A compared with group B. We could not detect any expression of AT2R in glomeruli in three groups. The PUs of Fas antigen and Bcl-2 protein in glomeruli in group A and B were was significantly correlated to glomerular sclerotic index (GSI) and GAI repectively.

Conclusion: In the process of gromerulosclerosis in adriamycin-induced nephrosis, glomerular cell apoptosis might be induced by the increased expression of Fas antigen and the decreased expression of Bcl-2 protein, but not the expression of AT2R. Enalapril interposing could ameliorate glomerulosclrosis, and partially reserving Bcl-2 expression in glomerular by which might inhibit glomerular cell apoptosis.

 
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