Effects of fluvastatin on renal fibrosis induced by cyclosporine A

Abstract:

Objective：To observe the effects of hydroxymethylglutaryl coenzyme A reductase inhibitor fluvastatin（Flu） on renal fibrosis induced by cyclosporine A（CsA） in rats． Methods：Totally 30 adult male SD rats were randomly divided into three groups．Controls were fed with olive oil，CsA treated rats were given CsA（30 mg/（kg·d）），and Flu treated rats were given CsA（30 mg/（kg·d）） and Flu（7 mg/（kg·d）） by gavage． Five rats of each group were sacrificed on the 14th d and the others were sacrificed at the end of the study（the 28th d）. Histological changes in renal tissue were observed． Sites and levels of expression of Smad protein 2/3，Smad protein 7 and transforming growth factor-β1（TGF-β1） were examined by immunohislochemistry staining． Renal function and lipid levels were measured in every week． Results：Serum creatinine（SCr） in Flu treated group on the 7th d was all equivalent to that of control group（P=0.564）． From the first week after treatment，levels of SCr in CsA treated group were significantly increased compared with those in control group（P＝0.000）． Compared with those of control group，Smad protein 2/3 and TGF-β1 expression on the 14th and 28th d was significantly increased in CsA treated rats（P＝0.000），while Smad protein 7 expression was markedly decreased（P＝0.000）． These lesions were significantly ameliorated by Flu. Levels of total cholesterol（P=0.865，0.997，0.505，0.871，0.540），triglyc－erides（P=0.894，0.663，0.826，0.635，0.928） had no statistical difference at same time point among all three groups. CsA valley con－centration had no statistical difference between Flu treated group and CsA treated group（P=0.183，P=0.123）． Conclusion：Flu could slow the progression of cyclosporine nephropathy.