氟伐他汀对肾衰大鼠肾脏纤维化病变进展影响及机制探讨

目的：探讨丙戊二酸辅酶A（HMG－CoA）还原酶抑制剂－氟伐他汀（Fluvastatin）在慢性进展性肾小球硬化和肾小管间质纤维化过程中圣贤有血管损伤、肾脏细胞外基质产生和降解过程中的影响。方法：采用5／6肾切除SD大鼠制备肾小球硬化及慢性肾衰实验动物模型，予氟伐他汀治疗后分别于治疗开始、治疗后第4周、第8周时间点观察大鼠血脂、尿蛋白、肾功能及血压变化，并评价该药对肾小球及小管间质组织病理学变化的干预作用。结果：氟伐他汀可降血压、减少蛋白尿、降低血脂、改善肾功能、防止和逆转肾血管硬化、狭窄。并通过影响PAI－1uPA等因子的表达而阻抑肾脏细胞外基质的产生，促进其降解。结论：提示氟伐他汀具有防治或改善慢性进行性肾小球硬化及间质纤维化的作用。

The Effects and Mechanism of Fluvastatin on Renal Fibratic Rats

Objective: To investigate the effects of Fluvastatin on renal vascular lesions and production and degradation of extracellular matix(ECM) during the evolution of glomerulosclerosis and tubulointerstitial fibrosis.Methods:5/6 nephrectomized SD rats were used as experimental model.At different time points after being treated with Fluvastatin,serum and urinary biochemical parameters, renal function and blood pressure were measured respectively. The effects of this agent on renal lesions were estimated by PAS and immunohistochemical staining.Results:Blood pressure,proteinuria, hyperlipidemia and renal function were improved significantly in treated group. The PAS staining showed that renal parenchymal and vascular damages improved markedly. The results of immunohistochenical staining showed that protein expression of PAI-1 in renal tissues decreased and uPA expression increased in the treated group.Conclusion: Fluvastatin has an important effect to improve the glomerulosclerosis and tubulointerstitial fibrosis.