妊娠相关血栓性微血管病(TMA)是一组临床急重症，严重威胁孕产妇及新生儿健康，肾脏是其最常受累的器官之一。该病发病机制复杂，涉及多种原因导致的血管内皮细胞损害。近年研究显示，补体系统的异常活化可能参与该病的发病。申请者的前期工作发现，妊娠相关TMA肾损害患者体内存在补体旁路途径的过度激活，且大多数患者体内血循环中存在补体H因子（旁路途径的调节蛋白之一）的水平低下及基因突变。由此，我们推测，H因子的功能缺陷可能与妊娠相关TMA肾损害的发生发展密切相关。本课题利用本中心充足的临床资源，拟通过对妊娠相关TMA肾损害患者循环及肾脏组织局部补体水平的检测、纯化患者血浆中H因子及相关功能研究、建立补体H因子基因缺陷的小鼠模型及利用妊高症的小鼠模型，动态关注妊娠相关TMA发病过程不同时期中补体活化的影响，深入阐明补体H因子在妊娠相关TMA肾损害中的参与机制，为未来该领域的“精准靶向治疗"提供理论依据。

Pregnancy-associated thrombotic microangiopathy (P-TMA) is a group of acute and severe clinical syndrome, which could be life-threatening conditions of pregnant and lying-in women and newborns. Kidney is one of the most commonly affected organs in the disease. Endothelial injury is the principal mechanism of disease underlying distinct forms of P-TMA. Recent studies suggested that disorder of complement system activation could be involved in the development of P-TMA. Our preliminary work found that the complement alternative pathway was over-activated in the patients with renal injury due to P-TMA, in whom the low levels of plasma complement factor H (CFH, the major regulator of the complement alternative pathway) and CFH gene mutants were also identified. Therefore, we proposed that the dysfunctions of CFH could contribute to the development of renal injury due to P-TMA. In this study, we planned to investigate the complement components in the plasma, urine and kidney tissues from P-TMA patients based on our well-defined cohort, purify CFH from the patients’ plasma and apply them for bio-functional studies, and generate CFH mutant knock-in mouse and pregnancy induced hypertension mouse models to mimic the development of P-TMA. Thus, we will assess the complement system activation in the progress of the disease, better understand the role of CFH in the pathogenesis of renal injury due to P-TMA, and provide evidence for the prospective “Precision Medicine” in the field.