活性维生素D_3对糖尿病大鼠肾脏TGF-β_1和HGF表达的影响

Effect of 1,25-dihydroxyvitamin D_3 on renal expression of TGF-1 and HGF in type 1 diabetic rats

目的:探讨活性维生素D3对糖尿病大鼠肾脏(Transforming growth factor-beta1,TGF-β1)和肝细胞生长因子(Hepatocyte growth factor,HGF)表达的影响。方法:雄性SD大鼠30只,按随机数字表法分为正常对照组(NC),糖尿病模型组(DM),活性维生素D3治疗组(DC),每组10只。12周后,观测肾组织形态学和肾功能变化,尿白蛋白排泄率等指标的变化,用免疫组化法检测肾脏TGF-β1表达水平的变化,RT-PCR法检测肾皮质TGF-β1mRNA、HGFmRNA表达水平的变化。结果:与NC组比较,第12周末DM组大鼠肾脏肥大指数(KW/BW)、平均肾小球体积(MGV)、系膜面积比(FMA)、尿白蛋白排泄率(UAER)、血肌酐(Scr)均明显升高(P<0.05),肾组织TGF-1mRNA及蛋白表达水平也显著升高(P<0.05),同时肾皮质HGFmRNA表达也有所增加(P<0.05)。DC组HGFmRNA的表达水平较DM组显著升高(P<0.05),而上述其他指标与DM组比较,则有明显的降低(P<0.05)。结论:活性维生素D3对于糖尿病肾脏病变至少具有部分保护作用,其机制可能为通过抑制糖尿病大鼠肾脏TGF-β1的过度表达,而上调HGF的表达,从而对糖尿病大鼠肾脏起保护作用。

Objective：To explore the effects of 1,25-dihydroxyvitamin D3 on renal expression of TGF-β1 and HGF in type 1 diabetic rats. Methods：30 Sprague-Dawley rats were randomized into 3 groups：normal control rats（group NC）,diabetic rats（group DM ） and diabetic rats treated with 1,25-dihydroxyvitamin D3（group DC）, Kidney-to-body weight ratio（KW/BW）,mean glomerular volume （MGV）, fractional mesangial area （ FMA ）, urinary albumin excretion rate （ UAER ）and serum creatinine （Scr）were measured after 12 weeks of treatment,while transforming growth factor-betal（TGF-β1） expression in kidney cortex were observed by imm unohistoehemistry. The expression levels of TGF-β1 mRNA and HGF mRNA were detected by reverse transcription and polymerase chain reaction（RT-PCR） at the end of the experiment. Results：UAER,Scr,MGV,FMA and KW/BW ratio were significantly higher in the diabetic rats than those in the normal control rats （P〈0.05）, The expression levels of TGF- β 1 and HGF in the diabetic rats were also higher as compared with those in the normal control group （P〈0.05）. UAER,Scr,MGV,FMA and KW/BW ratio and the expression levels of TGF-β1 in the 1,25-dihydroxyvitamin D3-treated group were obviously lower than those in the diabetic rats（P〈0.05）,while the levels of HGFmRNA in the 1,25-dihydroxyvitamin D3-treated group were obviously higher than in diabetic rats, Conclusion： 1,25-dihydroxyvitamin D3 has some renal protective effect on diabetes in rats,partly by down-regulating TGF-β1 and up-regulating HGF expressions in renal cortex