辛伐他汀抑制肾间质纤维化的实验研究

Experimental study of simvastatin for preventing renal interstitial fibrosis in rats

目的观察辛伐他汀在体内对细胞增殖、肾间质肿瘤坏死因子(TGF)-β1表达的影响。方法36只Wistar大鼠随机分为假手术组(SOR组,12只),模型对照组(UUO组,12只),辛伐他汀治疗组(SIM组,12只),SIM组术前1 d开始给予辛伐他汀20 mg.kg-1.d-1灌胃,其余两组以等量蒸馏水灌胃,术后14 d处死大鼠,留取血标本实验室检查血清胆固醇和甘油三酯,取术侧肾脏行HE、Masson染色比较各组肾组织病变,免疫组织化学SP法检测肾小管间质增殖细胞核抗原(PCNA)、TGF-β1的表达。结果SIM组肾组织纤维化病变减轻,肾小管间质细胞增殖受抑,TGF-β1表达下调。结论辛伐他汀能够抑制肾小管间质纤维化早期细胞的增殖,减少间质中炎性细胞的浸润,并通过下调TGF-β1的表达,削弱细胞增殖与细胞因子间相互促进的恶性循环来抑制肾小管间质纤维化的进展。

Objective To investigate the lipid - lowering - independent renoprotective effects of HRI. Metllmds Thirty-six Wistar rats were randomly distributed into 3 groups： sham operation group （SOR, n = 12）, unilateral ureteral obstruction group （UUO, n = 12） and simvastatin treatment group （SIM, n = 12）. SIM rats were treated with simvastatin （20 mg·kg^-1·d^-1 ） a day before operation, whereas the rest of rats with vehicles. All rats were killed at d 14 after operation. The samples of blcod were collected to detect the concentration of serum cholesterol and triglycerido. Immunohistochemistry was performed on renal tissue for proliferating cell nuclear antigen （PCNA） and transforming growth factor-beta 1 （TGF-β1 ）. Histological changes were aim observed by HE and Masson stain. Results Exprssion of PCNA and TGF-I3t in tubulointerstitium decreased in SIM group and there was significant difference between UUO and SIM （P 〈 0.05）. Conclusion Simvastatin ameliorate renal tubulointerstitial fibrosis through either inhibiting the proliferation or suppressing the expression of TGF-β1.