补体调节蛋白在特发性膜性肾病发病机制中的研究

Idiopathic membranous nephropathy (IMN), a common form of the nephrotic syndrome in adults, is an antibody-mediated glomerular disease, which pathogenesis has become an important research field. Triggers activation of complement system in situ deposition of immune complex in the glomerular epithelial cell, which is the important mechanism of podocyte damage. In physiological conditions, complement regulatory proteins that can block complement activation, is a class of important protein molecules, maintaining the balance of immune system. Thus, complement activation in membranous nephropathy mainly attribute to complement regulatory proteins dysfunction or its down-regulation. It is reported that the antigen, hybrid antigen (Fx1A), which induced animal model of membranous nephropathy, contained complement regulatory proteins. It could stimulate podocytes produce antibodies to inhibit podocyte complement regulatory proteins, resulting in complement activation. However, glomerular injury did not observed In animals induced by Fx1A without complement regulatory proteins. Furthermore, some kinds of complement regulatory proteins were found down-regulated in human podocytes. Based on this idea above, we put forward the hypothesis that CRP may protect podocytes from damage by complement activation, which will be a potential therapeutic target. This topic includes two parts, in vitro and in vivo experiments, in order to provide theoretical basis for clinical prevention and control of membranous nephropathy.

特发性膜性肾病（IMN）是抗体介导的器官特异性自身免疫性肾病，是导致成人肾病综合征的主要原因之一，其发病机制为目前研究重点。原位免疫复合物在肾小球上皮下沉积触发补体系统的活化，成为足细胞损伤的重要机制。正常情况下，抑制补体活化的补体调节蛋白（CRP）成为维持机体稳态平衡的重要分子，因此膜性肾病补体的活化可能是足细胞表面的CRP的减少或功能失调所致。文献报道，用于研究膜性肾病动物模型的诱导抗原——混合型抗原（Fx1A）含有CRP，刺激产生的抗体可抑制足细胞CRP而加剧补体活化，用剔除CRP的Fx1A免疫动物却不出现蛋白尿。同样，在人特发性膜性肾病中也发现足细胞某种CRP的表达明显减少。基于上述观点，我们提出设想，CRP可能是保护足细胞免于被补体活化损伤的重要分子，并作为一个可能的治疗靶点。本课题拟从体外和体内实验两部分进行论证，以期为临床膜性肾病的防治提供理论依据。