促肝细胞生长素对肾间质纤维化大鼠模型HGF、ALK5及TGF-β1表达的影响  

Effect of hepatocyte growth-promoting factors on the expression of HGF,ALK5 and TGF-β1 in rats with renal interstitial fibrosis

作　　者：陈丽平[1] 叶凡[2] 王保兴[2] 刘保良[1] 

机构地区：[1]河北医科大学第三医院药剂科,石家庄市050051 [2]河北医科大学第三医院肾内科,石家庄市050051

出　　处：《河北医药》2010年第13期1675-1678,共4页Hebei Medical Journal

摘　　要：目的研究促肝细胞生长素因子(pHGF)对肾间质纤维化大鼠肾组织中肝细胞生长(HGF)、转化生长因子-β1(TGF-β1)、活化素受体样激酶5(ALK5)及胶原Ⅲ的表达的影响,从而探讨促肝细胞生成素对肾间质纤维化的药物保护机制。方法 54只大鼠随机分为:假手术组、单侧输尿管结扎(UUO)组及pHGF治疗组。每组于术后第3、7、14天分批处死,分别经免疫组化方法测定肾小管间质中HGF、TGF-β1、ALK5、胶原Ⅲ的表达的情况,HE、MASSON染色评定3组肾小管间质损害程度。结果 UUO组TGF-β1、ALK5、胶原Ⅲ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治疗组明显低于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治疗组术后第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能有效抑制肾间质中TGF-β1,从而进一步抑制ALK5的过度表达、使胶原Ⅲ合成减少;同时促进肾间质中HGF表达,从而能够改善UUO大鼠肾间质纤维化的程度。Objective To investigate the effect of hepatocyte growth-promoting factors （pHGF） on the expression of HGF, ALKS, TGF-β1 and Co m in rats with renal interstitial fibrosis in order to explore the protective mechanism of pHGF on renal interstitial fibrosis. Methods 54 male Wistar rats were randomly divided into 3 groups： sham operation group, UUO group, UUO combined with HGF treatment （pHGF） group, and the rats were killed on the 3,7,14 days after surgery. The expressions of HGF, TGF-β1, ALK5, ColⅢ were detected by immunohistoehemical method, and the injury degree of kidney tubules interstitial tissue was examined by HE stain and Masson stain. Results The expressions of TGF-β1 , ALK5, Co Ⅲ and the injury degree of kidney tubules interstitial tissue in UUO group were increased significantly,as compared with those in sham operation group（ P 〈 0.05）. The pHGF group markedly limited the expression of TGF-β1,ALK5 and CoⅢ （ P 〈0.05）. In UUO group,the expression of HGF was the highest on the first three days, which decreased slightly on seven days and was the weakest on the first 14 days,as compared with that in UUO group. The expression of HGF in pHGF group after 3 days, 7 days, 14 days was significantly higher than that in UUO group（ P 〈 0. 05 ） , and the injury degree of kidney tubules interstitial tissue was significantly relieved, as compared with that in UUO group （ P 〈 0. 05 ）. Conclusion The pHGF can effectively inhibit the expression of TGF-β1 ,ALK5 and ColⅢ in renal interstitium of UUO rats, and HGF plays an protective role in renal interstitial fibrosis. The pHGF injection can lighten renal tubule extension, mononuelear-lymphocyte infiltration and deposition of collagen in renal interstitium.

关 键 词：肾间质纤维化 肝细胞生长因子 转化生长因子Β1 活化素受体样激酶5 胶原Ⅲ 促肝细胞生长素 

分 类 号：R692.33[医药卫生—泌尿科学]