阿魏酸钠对肾大部切除大鼠肾脏保护作用的研究

目的探讨阿魏酸钠对5/6肾切除大鼠肾脏病变的保护作用.方法大鼠随机分为4组,假手术组(Sham组),肾切除组(NX组),NX+阿魏酸钠组(SF组),NX+依那普利(E组).8周后检测大鼠血压、24h尿蛋白定量、血肌酐、BUN,肾皮质内皮素-1(ET-1)和一氧化氮(NO)等,观察肾组织病理改变,并应用RT-PCR的方法检测肾皮质内TGF-β1 mRNA的表达;Western蛋白印迹方法检测TGF-β1蛋白质的表达.结果术后大鼠出现明显的尿蛋白(201.2±4.1)mg/24h,肾皮质ET-1含量显著升高,且有明显的肾小球硬化,而阿魏酸钠和依那普利均能减少尿蛋白阿魏酸钠(78.1±3.1)mg/24h,依那普利(65.9±6.3)mg/24h,与假手术组比,P＜0.01],减少肾皮质ET-1含量和肾小球硬化指数.肾大部切除后肾皮质TGF-β1mRNA及其蛋白的表达明显升高,用药组上述指标明显降低(SF组和E组与NX组相比,P＜0.01).结论在5/6肾大部切除模型中,阿魏酸钠对5/6肾大部切除大鼠肾脏有明显的保护作用,其机制可能其减少肾脏ET-1的生成,抑制TGF-β1的表达有关.

Renoprotective effect of sodium ferulate on rats with 5/6 nephrectomy

Objective] To investigate the renopretective effect of sodium ferulate (SF) on rats with 5/6 nephrectomy. Methods] The rats were randomly assigned to four groups: sham-operation group(sham group), nephrectomy group (NX group), NX treated with sodium ferulate 50 mg/(kg.d) group (SP group), NX treated with enalapril 10mg/(kg. d) group (E group). The blood pressure, urinary protein for 24 hours (UP), serum creatinine, serum BUN, levels of endothelin-1(ET-1) and nitric oxide (NO) in renal cortex in rats as well as glomerulosclerosis index (GSI) were measured at the 8th week after operation, and the mRNA expression of TGF-β1 was detected by RT-PCR. The protein expression of TGF-β1 was detected by Western Blot. Results] Compared with sham group, the proteinuria,ET-1 and glomerulosclerosis index were significantly increased in the NX group UP: Sham (17.4±1.8) mg/24 h vs NX (201.2±4.1) mg/24 h, P＜0.01; GSI: Sham (1.9±0.7) vs NX (42.5±4.1), P ＜0.01]. Both of SF and enalapril could reduce the proteinuria, ET-1 and GSI UP: SF (78.4±3.1) mg/24 h, E (65.9±6.3) mg/24 h, vs NX, P＜0.01; GSI: SF (22.3±4.2), E (18.7±6.1); vs NX, P＜0.01]. Furthermore, the mRNA and protein expression of TGF-β1 in the NX group were significantly increased in NX model rats. SF and enalapril could decrease the expression of TGF-β1.Conclusion] SF has a significantly renoprotective effect on 5/6 nephrectomized rats, the mechanism might be related with its actions of reducing ET-1 production and inhibiting the expression of TGF-β1 in kidney.