阿魏酸钠对糖尿病大鼠肾脏的保护作用及机制研究

Renal Protective Effect and Its Mechanism of Sodium Ferulate in Diabetic Rats

目的 探讨阿魏酸钠(SF)对糖尿病(DM)大鼠肾脏的保护作用及机制。方法 对链脲佐菌素(STZ)诱导的DM大鼠灌胃给予SF 110mg/(kg·d),治疗8周,测定各组大鼠肾重/体重、血甘油三酯和胆固醇、肌酐清除率(Ccr)、24h尿蛋白、肾皮质内皮素-1(ET-1)和一氧化氮(NO)等,观察肾脏病理改变并用免疫组织化学方法检测肾组织转化生长因子-β1(TGF-β1)和Ⅳ型胶原的表达。并与正常组和DM模型组作比较。结果 与正常组比较,DM组大鼠肾重/体重、Ccr、24h尿蛋白、肾皮质ET-1显著升高(均P<0.01),肾脏病理学检查显著异常,TGF-β1和Ⅳ型胶原表达明显增高,SF组上述指标显著改善。结论 SF对DM大鼠肾脏具有保护作用,其机制可能与其减少肾脏ET-1的生成,抑制TGF-β1和Ⅳ型胶原的表达有关。

To study the renal protective effect of sodium ferulate (SF) and its mechanism in rats with diabetic mellitus (DM). Methods DM rats induced by streptozotocin were treated with SF 110 mg/kg per day for 8 weeks. The ratio of kidney weight/body weight (KW/BW), serum triglyceride (TG) and total cholesterol (TC), creatinine clearance rate (Ccr), urinary protein/24hrs, levels of endothelin-1 (ET-1) and nitric oxide (NO) in renal cortex in rats were measured, the pathological change of kidney were observed and the expression of transforming growth factor-β1(TGF-β1) and collagen Ⅳ(C-Ⅳ) in kidney were examined using immunohisto-chemical assay. The data obtained were compared with those obtained from untreated DM rats and normal rats respectively. Results Compared with the normal rats, in DM rats, Ccr, urinary protein/24 hrs, ET-1, expressions of TGF-β and C-Ⅳ were significantly increased in DM model rats (all P<0.01) , and significantly abnormal pathological change in kidney was found. While in the SF treated DM rats, the above-mentioned abnormal changes were all significantly improved. Conclusion SF has effect in protecting kidney of DM rats, the mechanism might be related with its actions of reducing ET-1 production in kidney and inhibiting the expressions of TGF-β and C-Ⅳ.