肝细胞生长因子及其受体在蛋白尿慢性肾纤维化大鼠肾组织中表达的动态变化

Expression of hepatocyte growth factor and c-Met in rats with chronic renal fibrosis

目的探讨蛋白尿慢性肾纤维化大鼠肾组织中肝细胞生长因子(HGF)及其受体c-Met表达和意义。方法36只♂SD大鼠随机分为对照组和蛋白尿慢性肾纤维化组,应用多柔比星(4mg/kg)尾静脉注射1周后重复的方法建立大鼠蛋白尿慢性肾纤维化模型,分别于第1次多柔比星注射后第4、7、10、13周末收集标本,观察大鼠24h尿蛋白、血清白蛋白(ALB)、血甘油三酯(TG)、总胆固醇(TC)及病理变化。应用Western blot与免疫组化技术分别检测肾组织HGF及c-Met蛋白表达。结果①模型组大鼠24h尿蛋白、ALB、TG、TC明显高于对照组(P<0.01)。②4周末时模型组尿蛋白较对照组明显增多,随着病程进展,肾小球硬化程度加重,第7周肾小球硬化呈局灶节段性分布,肾小球肥大,肾小囊扩张,肾小球有不同程度的硬化,间质可见明显纤维化和局灶性炎细胞。10周及13周肾纤维化程度及面积加重。③肾脏HGF及c-Met表达4周时较对照组增加(P<0.01),7周时开始降低,并随病程呈进一步降低。结论肾纤维化过程中,肾脏HGF及c-Met的表达早期上升是一种有益的防御反应;后期HGF、c-Met表达逐渐降低,肾纤维化逐渐发展。肾脏HGF及c-Met表达的下降可能是慢性肾纤维化发展的机制之一。

Objective To study the expression of hepatocyte growth factor（HGF）and its receptor c-Met in adriamycin-induced glomerulosclerosis rats model. Methods 36 male SD rats were randomly divided into the normal control group and chronic glomerulosclerosis rats model group induced by intravenous injection of adriamycin 4 mg/ kg, again after a week. At the end of 4 th,7 th, 10 th, 13 th week after the first injection, the sample were collected. The blood and urine biochemistry examination , pathological changes, the expression of HGF and c-Met were observed. Results ① 24 hours urine protein excretion, ALB, TG, TC in pathologic model rats gradully increased （ P 〈 0. 01 ）. ② At the 7th week, lightscope showed significant Bowman＇s capsule expansion, glomeruli hypertrophy, focal fibrosis in renal tubulointerstitium in glomerulosclerosis rats model group, and at the end of 10th and 13th weeks, these abnormal changes were obviously aggravated. ③ The productions of HGF and c-Met in the glomerulosclerosis model group rats, which were enhanced at the 4th week （ P 〈 0. 01 ）, decreased significantly at the 7th week, and were lower and lower as the renal fibrosis progressed. Conclusion In the pathogenesis of chronic renal fibrosis, HGF and c-Met levels initially increased but gradually declined. The decreased expression of HGF and c-Met in renal cortex of glomerulosclerosis model group rats might be one of the mechanisms of chronic renal fibrosis.