摘要
糖尿病肾病(DKD)是由糖尿病引发的肾脏微血管病变.足细胞是肾脏固有细胞中高度分化的上皮细胞类型之一,是维持肾小球滤过膜屏障通透性、完整性的重要组分.本文基于足细胞的病理和生理学特点,重点探讨黄芪甲苷(AS-Ⅳ)改善糖脂代谢紊乱诱导DKD足细胞凋亡、足细胞黏附障碍、足细胞分化、足细胞炎症、足细胞线粒体功能障碍和足细胞氧化应激的作用机制,发现AS-Ⅳ可介导CaN/NFAT、TUG1/TRAF5、miR-378/TRAF5、PPARγ/Klotho/FoxO1、p38-MAPK、PERK/ATF4/CHOP、ATF6、IRE1/JNK、Notch、AMPK/MTOR/p70S6K、ILK、Wnt/β-catenin、TGF-β1/Smads、NLRP3/Caspase-1/IL-1β、NF-κB、Sirt1/p53/Drpl、Nrf2/PINK1、Nrf2/ARE/TFAM和GSK-3β/Nrf2/HO-1等多种级联途径,恢复足细胞状态,有效延缓DKD的进展.
Abstract
Diabetic kidney disease(DKD)is a renal microvascular disease caused by diabetes.Podocyte is one of the highly differentiated epithelial cell types in the innate cells of the kidney,and are an important component in maintaining the permeability and integrity of the glomerular filtration membrane barrier.Based on the pathological and physiological characteristics of podocycles,this paper focuses on the mechanism of astragaloside(AS-Ⅳ)in improving the apoptosis of DKD podocycles,podocyclic adhesion disorder,podocyclic differentiation,podocyclic inflammation,podocytic mitochondrial dysfunction and podocytic oxidative stress induced by the disturbance of glucose and lipid metabolism.We found in this study that AS-Ⅳ could mediate multiple cascading pathways,such as CaN/NFAT,TUG1/TRAF5,miR-378/TRAF5,PPARγ/Klotho/FoxO1,p38-MAPK,PERK/ATF4/CHOP,ATF6,IRE1/JNK,Notch,AMPK/MTOR/p70S6K,ILK,Wnt/β-catenin,TGF-β1/Smasks,NLRP3/Caspase-1/IL-1β,NF-κB,Sirt1/p53/Drpl,Nrf2/PINK1,Nrf2/ARE/TFAM,and GSK-3β/Nrf2/HO-1,restoring the podocyte state and effectively delaying the progression of DKD.
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