抗纤灵抗大鼠肾间质纤维化的实验研究

目的探讨中药复方抗纤灵治疗大鼠单侧输尿管结扎（unilateral ureteral obstruction,UUO）所致肾纤维化的作用及机理。方法雄性SD大鼠18只随机分为3组，每组6只。用单侧输尿管结扎术建立大鼠肾纤维化模型，抗纤灵治疗2周后检测血肌酐、尿素氮含量等指标；HE染色和六胺银染色观察肾组织病变；采用RT-PCR和Western印迹分别检测转化生长因子-β1（transforming growth factor-β1，TGF-β1）、肝细胞生长因子（hepatocyte growth factor，HGF）mRNA和α-平滑肌肌动蛋白（α-smooth muscle actin,α-SMA）、TGF-β1受体（TβRⅠ及TβRⅡ）及肝细胞生长因子受体（C-Met）蛋白表达。结果与假手术组比较，模型组大鼠血肌酐、尿素氮均有明显上升；肾小球毛细血管基底膜明显增厚；肾组织TGF-β1 mRNA及α-SMA、TβRI、TβRⅡ、C-Met蛋白袁达显著上调，而HGF mRNA水平显著下调。中药干预后，血尿素氮含量显著降低，肾小球和肾小管基底膜仅见轻度增厚；肾组织α-SMA、TβRⅠ、TβRⅡ蛋白表达明显减少，HGF mRNA水平明显上调。结论抗纤灵可抑制肾组织α-SMA、TβRⅠ、TβRⅡ蛋白表达并增加肾纤维化保护性因子HGF mRNA的表达，从而改善梗阻性大鼠的肾间质纤维化及肾功能。

Experimental Study on Effect of Kangxianling on Rat Renal Interstitial Fibrosis

OBJECTIVE: To study the effect and mechanism of Kangxianling (KXL, a TCM herbal compound) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). METHODS: Eighteen male SD rats were randomly divided into 3 groups, 6 in each group, the sham operated group, the model group, and the KXL group. Renal interstitial fibrosis model was established in rats by UUO. After rats were raised for additional 14 days, their body weight, serum levels of creatinine (SCr) and blood urea nitrogen (BUN) were analyzed. Then rats were sacrificed, their renal pathology examined by HE staining and PASM staining; expressions of transforming growth factor-beta1 (TGF-beta1), hepatocyte growth factor (HGF) mRNA, and a-smooth muscle actin (alpha-SMA), TGF-beta1 receptor I (TbetaR I), TGF-beta1 receptor II (TbetaR II) and hepatocyte growth factor receptor (C-Met) protein in kidney tissue were determined by RT-PCR and Western blotting respectively. RESULTS: SCr and BUN in the model group were significantly higher than those in the sham operated group (P <0.05). Expressions of TGF-beta1 mRNA and a-SMA, TbetaR I , TbetaR II and C-Met protein in kidney tissue in the model group significantly up-regulated and mRNA expression of HGF significantly down-regulated, and obvious hyperplasia of the base member of glomeruli was seen. After intervention with KXL, BUN content significantly lowered, alpha-SMA, TbetaR I and TbetaR II protein expression decreased and HGF mRNA expression up-regulated significantly in the treated group, with slight pathological changes only shown as mild hyperplasia of the base member of glomeruli and renal tubules. CONCLUSION: KXL could inhibit the protein expressions of a-SMA, TbetaR I , TbetaR II and increase the mRNA expression of HGF, which is a protective factor against renal fibrosis. Therefore, it is effective in alleviating the renal interstitial fibrosis and improving the renal function in UUO rats.