中药干预膜性肾病相关信号通路研究进展

Research Progress in Chinese Medicine Intervention in Membranous Nephropathy-Associated Signaling Pathways

膜性肾病(Membranous nephropathy,MN)是引起成人肾病综合征最常见的病因之一。当前临床上常用来治疗MN的是激素类、免疫抑制类、细胞毒素类等药物,因其不良反应多、副作用大、复发率高广受诟病,因此更新当前治疗药物和治疗策略意义重大。既往研究表明,核转录因子-κB(NF-κB)、核因子E相关因子2(Nrf2)/血红蛋白氧合酶-1(HO-1)、调控细胞周期、促进细胞增殖、分化相关信号通路细胞外信号调节激酶(ERK)及调控细胞自噬相关信号通路[腺苷酸活化蛋白激酶(AMPK)/哺乳动物雷帕霉素靶蛋白(mTOR)、磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(AKT)/mTOR等信号通路]均与MN发生发展密切相关。同时,众多研究证实,中药可通过调控相关信号通路,调控IgG等免疫复合物沉积、改善足细胞损伤、提高足细胞自噬、减轻MN氧化应激和炎症反应,达到防治MN的目的,并具有安全性高、耐受性好、作用靶点多、复发率低、疗效确切的优势,能够更新当前MN治疗的药物和治疗策略。基于此,本文查阅了大量国内外最新研究报道,以期通过阐述上述相关信号通路在MN发生发展中发挥的作用及中药干预MN相关信号通路防治MN的最新研究进展,为MN防治的深入研究提供新思路与新方向,同时为临床上运用中医药防治MN提供理论依据与参考。

Membranous nephropathy(MN)is one of the most common causes of nephrotic syndrome in adults.At present,hormones,immunosuppressants,and cytotoxins commonly used in the clinical treatment of MN are widely criticized for adverse reactions,side effects,and high recurrence rate.Therefore,it is of great significance to update the current drugs and therapeutic options.Studies have shown that nuclear transcription factor-κB(NF-κB),nuclear factor erythroid 2-related factor 2(Nrf2)/hemoglobin oxygenase-1(HO-1),and the signaling pathways associated with the regulation of cell cycle,the promotion of cell proliferation and differentiation extracellular signal-regulated kinase(ERK)and the regulation of autophagy[e.g.,AMP-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)and phosphatidylinositol-3 kinase(PI3K)/protein kinase B(Akt)/mTOR]are closely related to the occurrence and development of MN.In addition,studies have confirmed that Chinese medicine can regulate the deposition of immune complexes such as IgG,alleviate podocyte injury,promote podocyte autophagy,and reduce oxidative stress and inflammatory response by modulating related signaling pathways,thereby preventing and treating MN.With high safety,good tolerance,multiple targets,low recurrence rate,and definite therapeutic effect,Chinese medicine can update the current drugs and therapeutic options for MN.By reviewing the latest research reports at home and abroad,this paper introduces the roles of the above-mentioned signaling pathways in the occurrence and development of MN and the recent research progress in the intervention of MN by Chinese medicine via these pathways,aiming to provide new ideas and directions for the in-depth study of MN prevention and treatment and provide a theoretical basis for the clinical application of traditional Chinese medicine in the prevention and treatment of MN.