胡芦巴碱对单侧输尿管梗阻大鼠肾组织TGF-β1 mRNA、ColⅠ、FN表达的影响

Effect of Trigonelline on the Expression of TGF-β1 mRNA,ColⅠ,FN in Kidney Tissue of Rat After Unilateral Ureteral Obstruction

目的观察胡芦巴碱(trigonelline)对单侧输尿管梗阻大鼠肾组织转化生长因子(TGF)-β1mRNA、胶原蛋白Ⅰ(ColⅠ)、纤维粘连蛋白(FN)表达的影响。方法采用单侧输尿管梗阻(UUO)诱导大鼠肾间质纤维化的动物模型,以依那普利为阳性对照药,将大鼠随机分为假手术组、模型组、依那普利组、胡芦巴碱高剂量组、中剂量组、低剂量组。术后第12天处死大鼠,收集血清测定肌酐(SCr)、尿素氮(BUN)、总胆固醇(CHO)、甘油三酯(TG)水平。采用原位杂交方法检测TGF-β1 mRNA,免疫组化方法检测大鼠肾间质组织细胞外基质(ECM)成分、ColⅠ、FN的表达。肾组织经HE、VG染色后,进行彩色病理图像分析,评定各组肾小管间质损害程度。结果UUO大鼠肾小管间质损伤指数及肾组织TGF-β1mRNA、ColⅠ、FN表达明显高于假手术组;胡芦巴碱与阳性对照药依那普利组比较,可使UUO大鼠肾小管间质损伤指数、肾组织中高表达的TGF-β1 mRNA、FN降低(P<0.05);并能降低UUO大鼠SCr、BUN、CHO、TG水平(P<0.05)。结论胡芦巴碱能下调TGF-β1 mRNA、Col Ⅰ、FN的表达,保护肾功能,减轻肾小管间质损伤、降低血脂、减少ECM合成,从而延缓了肾间质纤维化的形成。

OBJECTIVE To study the effect of trigonelline on the expression of transforming growth factor β1（TGF-β1）mRNA,Col-Ⅰ,FN in nephridial tissue of unilateral ureteral occlusion（UUO）rats.METHODS UUO rats were randomly divided into 6 groups,including sham,model,enalapril group and high-dose,mid-dose and low-dose trigonelline groups.The level of SCr,Bun,CHO and TG were determined from each group on the 12nd day.We used situ hybridization technology to measure the expression of TGF-β1 mRNA（TGF-β1 mRNA）and applied immunohistochemistry to measure the expression of ColⅠ,FN in renal interstitium.The tubulointerstitial damage of each group was evaluated by the graphic analysis system after the HE and VG stain.RESULTS In comparison with the sham group,the tubulointerstitial damage index and the expression of TGF-β1 mRNA,ColⅠ,FN in the UUO rats were significantly increased.Compared with the enalapril group,the tubulointerstitial damage index and the high expression of TGF-β1 mRNA,FN in the trigonelline groups decreased（P〈0.05）.The level of SCr,BUN,CHO and TG decreased（P〈0.05）.CONCLUSION Trigonelline may reduce the tubulointerstitial damage index,then decrease the synthesis of ECM and reduce the renal interstitial fibrosis through inhibiting the expression of TGF-β1 mRNA,ColⅠand FN.