中文摘要
C5b-9膜攻击复合物诱导的足细胞损伤是特发性膜性肾病(Idiopathic membranous nephropathy,IMN)的主要病理表现。我们及同行研究发现:Wnt/β-catenin信号通路的活化在促进足细胞损伤中发挥关键作用,同时自噬活性增强对足细胞起到保护作用。实验研究表明:Wnt信号通路的活化可以抑制自噬。课题组从少阴太阴合病入手,临床发现麻黄附子甘草汤合肾着汤治疗IMN可显著减少患者蛋白尿,提高血浆白蛋白水平。因此,我们提出如下假说,该方可通过抑制Wnt/β-catenin信号通路的活化来激活自噬,对抗IMN足细胞损伤。本研究拟以C5b-9复合物诱导的足细胞损伤模型和被动型Heymann肾炎大鼠模型为研究对象,用上方干预后观察Wnt/β-catenin信号通路变化,并进而探讨其对自噬活性和足细胞的影响,为揭示该方的作用机制和在临床中推广应用经方治疗IMN提供科学依据。
英文摘要
The podocyte damage induced by C5b-9 compounds is the main pathological manifestations of idiopathic membranous nephropathy(IMN). We found that the Wnt/beta-catenin signaling pathway play an important role in the process.At the same time,increased activity of autophagy can protect podocyte from injury. It also show that the activation of Wnt signaling pathway can inhibit autophagy,which stated in vitro experiments. Our team start with shaoyin combined with taiyin,and pervious clinical studies found that the treatments based on mahuang fuzi gancao tang and shenzhuo tang can reduce urine protein and improve the level of plasma albumin in IMN patients. Therefore,we posit that this medical prescription could activate autophagy and induced IMN podocyte injury by suppressing the activation of Wnt/beta-catenin signaling pathway.We reserch on the podocyte damage cell-model induced by C5b-9 compounds and the passive heymann nephritis(PHN) model rats , in order to observe the Wnt/beta-catenin signaling pathway change after used the medical prescription,and then investigate its effection on the autophagic activity and the damage podocyte, providing scientific basis for the mechanism and further application of the traditional presciotion in IMN.
