促肝细胞生长素对单侧输尿管结扎大鼠肾间质纤维化的干预作用

目的研究促肝细胞生长素（pHGF）对肾间质纤维化大鼠肾组织中HGF、TGF-β1的表达的影响及其改善肾小管间质纤维化可能的机制，为临床防治肾间质纤维化提供实验性理论依据。方法采用单侧输尿管结扎术（unilateral ureteral obstruction UUO）建立肾小管间质纤维化大鼠模型。将54只大鼠随机分为三组：假手术组，UUO组，pHGF干预组。术后3、7、14天分3批处死各组大鼠，分别经免疫组化方法观察各组大鼠肾组织HGF、TGF-β1的表达情况，HE及Masson染色评定各组肾小管间质损害程度。结果UUO组TGF-β1的表达及肾小管间质损伤程度明显高于假手术组（P〈0．05）；而pHGF干预组明显低于UUO组（P〈0．05）；UUO组HGF于第3天表达最高，第7天稍有回落，第14天表达最弱；pHGF干预组术后第3天、第7天、第14天HGF的表达均显著高于同时期UUO组（P〈0．05），肾小管间质病变程度明显减轻，肾间质相对面积显著减小（P〈0．05）。结论pHGF能够减轻单侧输尿管结扎大鼠肾间质纤维化的程度，这种作用可能通过有效抑制肾间质中TGF-β1的过度表达、促进肾间质HGF的表达而实现。

Interventional effect of hepatocyte growth-promoting factor on interstitial fibrosis in rat kidney after ligation of unilateral ureter

Objective To study the effects of hepatocyte growth-promoting factor （pHGF） on the expression of hepatocyte growth factor （HGF） and transforming growth factor β1 （TGF-β1） in rat kidney with interstitial fibrosis, and to explore the possible mechanism of pHGF in the improvement of renal interstitial fibrosis in rats for providing useful clues to the prevention and treatment of clinical renal fibrosis. Methods Fifty-four male Wistar rats were randomly divided into 3 groups： sham operation group, unilateral ureteral obstruction （UUO） group, and UUO treated with pHGF （UUO ＋ pHGF） group. Rats were sacrificed after the surgery for 3, 7 and 14 days. Histological change in the obstructed kidney was observed by HE stain and Masson stain. HGF and TGF-β1 in tissues were examined by immunohistochemical method. Results, TGF-β1 expression and injury in tubular interstitium were more prominent in UUO group than in sham operation group （P 〈 0.05） and in UUO ＋ pHGF group （P 〈 0.05）. In UUO group, HGF expression in kidney was high in the first 3 days after the surgery, decreased at 7th day, and then became weaker at 14th day after the surgery. In UUO ＋ pHGF group, however, HGF expression was higher than that in UUO group at 3^rd, 7^th and 14^th day after the surgery （P 〈 0.05）, in association with less pathological change and smaller area of tubulointestitial injury （P 〈 0.05）. Conclusion pHGF improves the tubulointerstitial injury due to ureteral obstruction in rats, possibly through the inhibition of TGF-β1 over-expression and stimulation of HGF expression in renal interstitium.