基于调控足细胞程序性死亡的中药治疗膜性肾病药理机制研究进展

Research progress on the pharmacological mechanism of traditional Chinese medicine in the treatment of membranous nephropathy based on regulating podocyte programmed death

膜性肾病(membranous nephropathy,MN)是一种以上皮下免疫复合物沉积为典型病理特征的原发性肾小球疾病,其核心机制为免疫复合物沉积进而所造成的足细胞损伤。目前包括糖皮质激素联合免疫抑制药物或生物制剂在内的MN主流治疗方案,存在疗效个体差异较大、停药容易复发及不良反应多等局限性。近年来MN中的足细胞程序性死亡异常在疾病发生发展过程中的潜在作用越来越被重视。中医药对此相关的基础研究也大量展开。当前研究表明,中药单体、中药复方、中成药等可通过磷脂酰肌醇-3-激酶(phosphatidylin-ositol-3-kinase,PI3K)/蛋白激酶B(protein kinase B,AKT)信号通路、核因子E2相关因子(nuclear factor erythroid-derived factor 2-related factor,Nrf2)信号通路、丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)信号通路、细胞核转录因子(nuclear factor kappa-B,NF-κB)信号通路、富含亮氨酸重复蛋白3(leucine-rich repetitive protein 3,NLRP3)/天冬氨酸蛋白水解酶1(Caspase-1)信号通路等,调控包括足细胞自噬、调亡、焦亡、铁死亡等一系列细胞程序性死亡过程,进而缓解足细胞损伤,保护肾脏功能。本文从中药单体、中药复方和中成药的角度对干预相关靶点通路治疗MN有关文献进行总结,旨在为中医药抗MN的临床治疗、基础研究及靶向药物的研发提供一定的参考依据。

Membranous nephropathy(MN)is a primary glomerular disease characterized by the deposition of subcutaneous immune complexes as a typical pathological feature.Its core mechanism is the foot cell damage caused by the deposition of immune complexes.Currently,mainstream treatment options for MN,including glucocorticoids combined with immunosuppressive drugs or biological agents,have limitations such as significant individual differences in efficacy,easy recurrence after discontinuation,and multiple adverse reactions.In recent years,the potential role of abnormal programmed cell death in membranous nephropathy has been recognized increasingly.Basic research related to traditional Chinese medicine has also been extensively conducted.Current research shows that Chinese medicine monomer,Chinese medicine compound,traditional Chinese patent medicines and simple preparations,etc.can regulate a series of programmed cell death processes including podocyte autophagy,apoptosis,pyroptosis,and ferroptosis,thereby alleviating podocyte damage and protecting kidney function via PI3K/AKT,Nrf2,MAPK,NF-κB and NLRP3/Caspase-1.This article summarizes the literature on the treatment of membranous nephropathy by intervention related target pathways from the perspective of Chinese medicine monomer,Chinese medicine compound and traditional Chinese patent medicines,aiming to provide some references for the clinical treatment,basic research and development of targeted drugs of Chinese medicine for membranous nephropathy.