基于中医和法对TGF-β1/BMP7/Gremlin通路串话的再平衡探讨扶肾方抗腹膜纤维化的机制研究

Peritoneal fibrosis(Peritoneal fibrosis, PF) is a common complication of longtime peritoneal dialysis, peritoneal ultrafiltration and the transport can lead to failure, loss of peritoneal structure, function.Therefore, it is necessary to explore the molecular mechanism of intervention can even reverFse the process of PF, while BMP7 and Gremlin are expected to become targets for anti PF drugs.Overexpression of Gremlin and organ fibrosis are impDortant relationship. Such as lung, kidney, liver and peritoneum.TransdifferePntiation of mesothelial cell(EMT) is the initial part and the reversible part of PF, its effective regulation of EMT, it can prevent and even reverse the early PF suppression. BMP-7 .is one of the most important factors can be reversed EMT process, has now been confirmed.TGF-β1, antagonist TGF-β1 anti fibrosis factor BMP-7. Endogenous antagonist of BMP-7 is Gremlin. BMP- 7 and Gremlin imbalances in the body, which is the important mechanism of the cause organ fibrosis development. Department of nephropathy First Hospital Affiliated to Tianjin Medical University of the creation of he"Fushen decoction", it takes the traditional Chinese medicine peace law as the total principle."Fushen decoction" can regulate the TGF-β 1 and other EMT related active substances inhibitory PF.It has been used in the past by the National Natural Science Fund project to study confirmed.This project is a continuation of previous studies.It puts forward a point of view："The Fushen decoction regulation of TGF-β1/BMP7/Gremlin signaling pathway and balance the influence to EMT process intervention of peritoneal fibrosis"This subject adopts .experiments in vivo and in vitro, and pathology and molecular biology techniques.This topic wants to explain: "Fushendecoction" to the prevention and treatment of peritoneal mesothelial cells of EMT mechanism, the delay of the PF,which is of great significance in improving the curative effect of long time peritoneal dialysis.

腹膜纤维化(PF)作为长程腹透常见并发症， 可导致腹膜超滤与转运功能衰竭， 腹膜结构、功能丧失；间皮细胞表型转分化（EMT）是PF起始和可逆环节，有效调控EMT可阻抑甚至逆转早期PF。 而骨形态发生蛋白-7即BMP7和Gremlin有望成为抗PF治疗靶点： BMP-7目前被证实为拮抗致纤因子TGF-β1、逆转EMT的最重要因子之一； Gremlin为BMP-7内源性拮抗剂，其过度表达与肺、肝、肾、腹膜等器官的纤维化有关；此三者在体内失衡是引起器官纤维化发生发展的重要机制。既往项目研究证实扶肾方以中医学“和法”理论为宗，通过调控EMT相关活性物质阻抑PF。本课题基于此提出假说： “扶肾方基于中医和法，通过调控TGF-β1/BMP7/ Gremlin信号传话再平衡，进而阻抑PMCsEMT及PF进程”。本课题将采用病理、分子生物学技术，对在干预EMT及PF的机制及应用于PD治疗的意义给出阐释。

腹膜纤维化（PF）作为长程腹透常见并发症， 可导致腹膜超滤与转运功能衰竭， 腹膜结构、功能丧失；间皮细胞表型转分化（EMT）是PF起始和可逆环节，有效调控EMT可阻抑甚至逆转早期PF。 BMP-7目前被证实为拮抗致纤因子TGF-β1、逆转EMT的最重要因子之一； Gremlin为BMP-7内源性拮抗剂，其过度表达与肺、肝、肾、腹膜等器官的纤维化有关；此三者在体内失衡是引起器官纤维化发生发展的重要机制。既往项目研究证实扶肾方以中医学“和法”理论为宗，通过调控EMT相关活性物质阻抑PF。本课题基于此提出假说： “扶肾方基于中医和法，通过调控TGF-β1/BMP7/ Gremlin信号传话再平衡，进而阻抑PMCsEMT及PF进程”。研究结果证明：在体实验和证明扶肾方可有效干预腹膜纤维化进程，抑制了TGF-β1和Gremlin的表达，提高了BMP7的表达，并且与剂量呈正相关；离题实验发现：抑制了TGF-β1和Gremlin的表达，提高了BMP7的表达，促使细胞炎症反应有一定程度的减轻。