促肝细胞生长素改善单侧输尿管梗阻大鼠肾脏纤维化的研究

Improvement of renal fibrosis by pHGF in rat obstructive nephropathy

目的:研究促肝细胞生长素(hepatocyte growth-promoting factor,pHGF)改善梗阻性肾病肾小管间质纤维化的疗效和机制。方法:17只SD大鼠随机分为假手术组(SOR)、单侧输尿管梗阻组(UUO)和pHGF治疗组。给药组用促肝细胞生长素pHGF(30μg.kg-1.d-1)大鼠腹腔注射,其余组给予等剂量生理盐水。14 d后收获大鼠。通过测定肾皮质羟脯氨酸含量比较纤维化改变;肾脏病理分析用H.E.和Masson染色,免疫组化检测TGF-β1,α-SMA,FN在肾组织中的表达。结果:肾组织羟脯氨酸定量UUO组明显高于SOR组,pHGF组,pHGF组介于二者之间,P(0.01;Masson染色SOR组仅在血管和基底膜处有绿染的胶原纤维,UUO组胶原成分增多,而pHGF组较UUO组明显改善,P(0.01。免疫组化显示pHGF能明显降低梗阻肾组织TGF-β1,α-SMA,FN的表达水平降低,与UUO组比较,P(0.01。结论:pHGF能有效缓解梗阻性肾病肾小管间质纤维化。

Aim：To investigate the protective effect of hepatocyte growth-promoting factor （pHGF） against interstitial inflammation and the fibrosis development. Methods： Rat were randomly assigned to sham-operation group（SOR）, Unilateral ureteral obstruction group （UUO）, pHGF treated group （pHGF）. The pHGF treated group rats were administered pHGF 30 μg · kg^-1 · d^-1 by peritoneal injection, others with normal saline. 14 days after unilateral ureteral obstruction, renal fibrosis was assessed by measuring cortex hydroxyproline content. Renal pathology was assessed by Hematoxylin-eosin （H. E. ） stain and Masson stain. TGF-1β, α-SMA, FN in the cortical interstitium was examined by immunohisto- chemically. Results： pHGF protected against the renal interstitial fibrosis elicited after ureteral obstruction, P 〈 0. 01. Conclusion ：These results indicate that pHGF can efficiently ameliorate renal interstitial fibrosis in this model, and suggest that pHGF have clinical potential in the management of the obstructive nephropathy.