肝细胞生长因子在大鼠肾间质纤维化中作用机制的研究

Role of hepatocyte growth factor in renal interstitial fibrosis in unilateral ureteral obstruction rats

目的 :通过观察大鼠单侧输尿管梗阻 (UUO)后 ,肝细胞生长因子 (HGF)的表达及其与转化生长因子 β1(TGF β1)之间的动态变化关系 ,以探讨HGF在肾间质纤维化中的作用机制。 方法 :将 36只雄性SD大鼠中的 18只行左侧输尿管结扎术 ,另外 18只行假手术。于术后第 3、7、14天分别处死各组中的 6只大鼠 ,用免疫组化方法测定HGF、TGF β1、α 平滑肌肌动蛋白 (α SMA)及纤维粘连蛋白 (FN)的表达 ,并行苏木精 伊红 (H E)和Masson染色 ,动态观察肾的病理学改变。 结果 :在肾间质纤维化早期 ,肾HGF表达明显增加而TGF β1表达却明显下降 ;在肾间质纤维化晚期 ,肾HGF表达明显下降而TGF β1表达却明显上升 ,同时α SMA和FN的表达明显增强 ,肾的病理改变明显 ,而且HGF表达与TGF β1、α SMA及FN表达呈明显负相关。 结论 :HGF可能是肾间质纤维化进程中重要的调节因子 ,它与TGF β1相互作用 ,共同调节肾间质纤维化的发生和发展。

Objective:To study the role of hepatocyte growth factor(HGF)in the process of renal interstitial fibrosis caused by unilateral ureteral obstruction(UUO)in rats, and to study the correlation between HGF and transforming growth factor-β 1(TGF-β 1). Methods:Eighteen Spraque-Darley rats were subjected to UUO, and additional eighteen rats were sham operated.Six rats of each group were killed respectively at 3, 7, 14 days after surgery.Immunohistochemistry study was performed on renal tissue for HGF, TGF-β 1, α-smooth muscle actin(α-SMA), and fibronectin. Histological changes were also observed by HE ang Masson staining. Results:In the early stage of renal interstitial fibrosis, expression of renal HGF increased significantly, whereas expression of TGF-β 1 decreased significantly. In advanced stage, expression of renal HGF decreased , whereas expression of TGF-β 1 increased. The expression of HGF was negatively correlated with the expression of TGF-β 1,α-SMA and FN . Conclusion:HGF may play a crucial role in the process of renal interstitial fibrosis. TGF-β 1 level increasing and local HGF expression decreasing may be responsible for the progression of renal interstitial fibrosis.