肝细胞生长因子在大鼠肾小管间质纤维化中的表达及意义

目的探讨肝细胞生长因子(HGF)在肾小管间质纤维化过程中的表达及意义。方法雄性3月龄SD大鼠60只,随机分为对照组和模型组各30只,以腺嘌呤灌胃法建立大鼠肾小管间质纤维化模型,对照组以等体积的2%淀粉溶液灌胃,分别于实验第7周、12周、17周时随机处死10只大鼠,进行血肌酐(Cr)、血尿素氮(BUN),24 h尿蛋白定量和尿NAG酶检测,光镜下观察肾组织的病理变化及免疫组织化学法检测肾脏HGF、转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(-αSMA)的表达情况。结果与对照组比较,模型组各时相点大鼠尿蛋白、尿NAG酶、血Cr及血BUN均升高(P<0.01);7周时模型组即有肾小管间质损害,随着病程进展,肾小管间质损害逐渐加重;肾脏HGF表达7周、12周时增加,17周时降低;与TGF-β1、α-SMA表达呈负相关(r=-0.999,P<0.01;r=-0.980,P<0.01)。结论肾小管间质纤维化过程中,肾脏HGF的表达早期上升是一种有益的防御反应。HGF抑制TGF-β1、α-SMA的表达,发挥其抗纤维化作用。

Expression and significant of hepatocyte growth factor in renal tubulointerstitial fibrosis in rat

Objective To probee the significance of expression of hepatocyte growth factor(HGF) in tubulointerstitial fibrosis of rat.Methods Sixty male SD rats,aged three months,were randomly divided into two groups: control group(n=30),model group(n=30).The tubulointerstitial fibrosis model was induced by gavage with adenine in model group,and the same volume 2% tarch solution was given by gavage in control group.At the 7th,12th and 17th week,ten rats in every group were sacrificed.The urinary protein,N-acetyl-β-D-glucosaminidase(NAG) in the urine and renal profile including BUN and Cr was examined.The histological changes of kidney were observed by light microscopy,and the expression of HGF,transforming growth factor-beta 1(TGF-β_1) and α-smooth muscle actin(α-SMA) were examined by immunohistochemistrical method.Results At the 7th,12th and 17th week,the value of urinary protein,NAG,serum BUN and Cr of rats in model group were higher than those in control group(P<0.01). Renal interstitium injury was demonstrated in model group rats at the 7th week, and became aggravating after 7 weeks.At the 7th and 12th week,the expression of HGF in rats of model group were higher than that of control group.The expression of HGF decreased gradually,and was the lowest in the 17th week.There was negative correlation between expressions of HGF,TGF-β_1 and α-SMA(r=-0.999,P<0.01;r=-0.980,P<0.01).Conclusion Elevated expression of HGF at the early stage is a beneficial response during renal tubulointerstitial fibrosis.Endogenous HGF may exert antifibrotic effect by inhibiting expression of TGF-β_1 and α-SMA.