Effect of simvastatin on experimental interstitial fibrosis and its mechanism / 中华肾脏病杂志

ABSTRACT

Objective To evaluate the effect and mechanism of HMG-CoA reductase inhibitor simvastatin on experimental interstitial fibrosis. Methods Experiments on rat 5/6 nephrectomy chronic renal failure model and primary cultured renal interstitial fibroblast cells were conducted in this study. The cell proliferation, extracellular matrix, c-fos mRNA expression of rat interstitial fibroblasts were measured by MTT assay, immunohistochernitry, semi-quantitative reverse-transcript PCR methods, respectively. Results Serum cholesterol, triglyceride and creatinine of treated group were significantly reduced by simvastatin as compared with controls. No statistical significance in BUN was observed between untreated and simvastatin-treated rats. Histological examination revealed that simvastatin caused a reduction in the glomeruli with sclerosis. Tubulointerstitial injury paralleled the degree of glomerular damage. Simvastatin in a dose-dependent manner inhibited the proliferation of renal intersititial fibroblasts, decreased the secretion of lamimn( LN), and suppressed the expression of c-fos mRNA, as compared with normal controls. No obvious effect on hyaluronic acid( HA) secretion of fibroblasts was found. Conclusions Simvastatin is anti-proliferative in interstitial fibroblasts and decreases the secretion of laminin. This effect is exerted, at least in part, via inhibition of the c-fos and c-jun-dependent mitogenic pathway. Simvastatin may prevent interstitial fibrosis development and attenuate renal damage in uremic rats with hvperlipidemia.