大黄附子汤加减方治疗慢性肾衰竭大鼠的疗效机制研究

Study on the Therapeutic Mechanism of Dahuang Fuzi Decoction in theTreatment of Chronic Renal Failure Rats

目的:以Wnt/β-catenin信号通路为切入点,观察大黄附子汤加减方对慢性肾衰竭大鼠一般情况、贫血状况、肾功能、纤维化因子的影响,探讨该方治疗CRF的疗效机制。方法:将80只雄性Wistar大鼠随机选取40只分为空白组、假手术组,其余40只为造模组,并经5/6肾切除术后随机分为模型组、大黄附子汤加减方组。造模完成后4周始,空白组、模型组、假手术组大鼠予生理盐水灌胃,大黄附子汤加减方汤组予大黄附子汤加减方中药液灌胃;治疗后观察各组肾组织病理变化、免疫功能指标及肾功能指标。结果:与空白组比较,模型组大鼠SCr、BUN,以及肾组织Wnt4、β-catenin、TCF1、LEF1、MMP-7表达水平均显著升高(P<0.05),RBC、Hb含量均显著降低(P<0.05)。与模型组比较,大黄附子汤加减方组大鼠SCr、BUN,以及肾组织Wnt4、β-catenin、TCF1、LEF1、MMP-7表达水平均显著降低(P<0.05);RBC和Hb含量显著升高(P<0.05)。结论:大黄附子汤加减方可有效改善CRF大鼠的一般情况、贫血状况、肾脏功能,并能抑制Wnt/β-catnin通路发生活化,下调Wnt4、β-catenin、MMP-7、TCF1、LEF1的表达,减轻肾纤维化程度,延缓CRF病程进展。

Objective:Taking Wnt/β-catenin signaling pathway as the breakthrough point,to observe the effect of modified Dahuang Fuzi Decoction on the general condition,anemia status,renal function,and fibrosis factors of chronic renal failure rats,and to explore the therapeutic mechanism of this decoction in the treatment of CRF.Methods:80 male Wistar rats were randomly divided into a blank group and a sham operation group,and the remaining 40 rats were used as the model group.After 5/6 nephrectomy,they were randomly divided into the model group and Dahuang Fuzi Decoction group.Four weeks after the completion of the model,the rats in the blank group,the model group,and the sham operation group were given normal saline by gavage,and the rats in the Dahuang Fuzi Decoction group were given Dahuang Fuzi Decoction by gavage.After treatment,the pathological changes in renal tissue,immune function indexes,and renal function indexes of each group were observed.Results:Compared with the blank group,the SCr,BUN,and the expression levels of Wnt4,β-catenin,TCF1,LEF1,and MMP-7 in the renal tissue of the model group were significantly increased(P<0.05),and the contents of RBC and Hb were significantly decreased(P<0.05).Compared with the model group,the expression levels of SCr,BUN and Wnt4,β-catenin,TCF1,LEF1,and MMP-7 in renal tissue of rats in the Dahuang Fuzi Decoction group were significantly decreased(P<0.05).RBC and Hb content increased significantly(P<0.05).Conclusion:Dahuang Fuzi Decoction can effectively improve the general condition,anemia,and renal function of CRF rats,inhibit the activation of the Wnt/β-catenin pathway,down-regulate the expression of Wnt4,β-catenin,MMP-7,TCF1,and LEF1,reduce the degree of renal fibrosis and delay the process of CRF.