关键词: 环孢素A, 肾毒性, 核因子κB

Abstract: AIM: This study was to ascertain the role of NF κB in cyclosporine A( CsA)-induced nephrotoxicity and relations between TGF β1,caspase3 and apoptosis . Methods: 64 wistar male rats were randomly divided into 4 groups of sixteen rats as follows. Vehicle，PDTC，CsA，CsA ＋ PDTC. rats received a daily subcutaneous injection of CsA 15 mg.kg－1.d－1 ，and a daily subcutaneous injection of CsA 15 mg.kg－1.d－1 and PDTC 100mg.kg－1.d－1. BUN,serum creatinine, N-acetyl-beta-d-glucosaminidase (NAG) and urine routines were examined. The kidneys were processed for light microscopy,immunocytochemistry and TENUL. Results: A rat model of CsA-induced nephrotoxicity was established observed from light microscopy. CsA groups significantly increased the values of the BUN, SCr and urine NAG compared with the controls whereas CsA ＋ PDTC group not. Immunohistochemistry revealed that the expressions of protein NF κB, TGF β1, caspase3 increased significantly in CsA-treated rats compared with conrtol ,whereas the expressions of protein NF κB, TGF β1, caspase3 was inhibited by PDTC. Apoptosis is observered in the CsA-induced chronic nephrotoxicity by TUNEL, PDTC blocked the apoptosis caused by CsA. Conclusions: CsA-induced chronic nephrotoxicity mainly include injuries of tubules,accompanied vacuolation, nucleus pycnosis and destroyed structures ,glomerulus injury also can be observed. Apoptosis is induced in the CsA-induced chronic nephrotoxicity and caspase3 may be involved in the regulation of this apoptosis，Inhibition of NF κB blockaded apoptosis in CsA-induced chronic nephrotoxicity . CsA induced up-regulated the expression of TGF β1 and significantly reduced the expression with PDTC. It is suggested that NF κB plays important roles in progression of chronic CsA nephrotoxicity and regulates other factors

Key words: cyclosporin A, nephrotoxicity, nuclear factor kappa B