活血祛瘀方对单侧输尿管梗阻大鼠肾间质细胞外基质的调节

Regulation of "Huoxue Quyu recip" on Extracellular Matrix in Rats after Unilateral Ureteral Obstruction

目的:通过研究中药复方活血祛瘀方对单侧输尿管梗阻(UUO)大鼠肾组织α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白(FN)、纤溶酶原激活物抑制剂-1(PAI-1)及肝细胞生长因子(HGF)表达的影响,探讨其对细胞外基质(ECM)的调节机制。方法:建立大鼠UUO模型,48只SD大鼠随机分为假手术组、模型组、代文组、活血祛瘀方组,于治疗4周后取梗阻侧肾组织,免疫组织化学染色观察α-SMA、FN、PAI-1及HGF的阳性染色表达,并进行半定量分析。结果:与假手术组相比,模型组大鼠α-SMA、FN、PAI-1阳性表达显著升高(P<0.01)。与模型组相比,活血祛瘀方组肾间质α-SMA、FN及PAI-1阳性表达显著下调(P<0.01),而HGF阳性表达则显著上调(P<0.01)。结论:活血祛瘀方可抑制肾组织α-SMA、FN及PAI-1过度表达,诱导HGF高表达,从而减少ECM的过度聚集,这可能是活血祛瘀方抗肾间质纤维化的作用机制之一。

Objective：To investigate the effects of ＂Huoxue Quyu recip＂ ,a compound traditional Chinese herbal medicine,on expression of alpha-smooth muscle actin（ α-SMA） ,fibronectin（ FN） 、plasminogen activator inhibitor-1（ PAI-1） and hepa-tocyte growth factor（ HGF） in renal tissue of rats with unilateral ureteral obstruction（ UUO） and to illuminate the regulation mechanisms of extracellular matrix（ ECM）. Methods：48 Sprague-Dawley rats were unilaterally obstructed by ligation of the proximal u-reters and randomly divided into sham-operated group,model group,Diovan treated group,and ＂Huoxue Quyu recip＂ treated groups. The rats were sacrificed on the 4th week after treatment,and immunohistochemistry staining for semiquantitative analysis of α -SMA、FN、PAI-1 and HGF. Results：The lever of α -SMA、FN and PAI-1 in model group increased as compared with those in the sham-operated group（ P 0. 01） 。In comparison with the model group,the expression of positive staining for α-SMA、FN and PAI-1 in ＂Huoxue Quyu recip＂ treated group were significantly down-regulated（ P 0. 01） ; but the expression of HGF were significantly up-regulated（ P 0. 01）. Conclusion：＂Huoxue Quyu recip＂ could decrease the excessive aggregation of ECM via inhibiting the protein expressions of α-SMA、FN and PAI-1,inducing the expression of HGF,which may explain one of the mechanisms of its antifibrotic effect.