盐皮质激素受体拮抗剂治疗糖尿病足细胞损伤的研究进展  

Advances of mineralocorticoid receptor antagonists treating diabetic podocyte injury

作　　者：杨柳(综述) 张炯(审校) YANG Liu;ZHANG Jiong(National Clinical Research Center for Kidney Diseases,Jinling Hospital,Nanjing 210016,China)

机构地区：[1]东部战区总医院国家肾脏疾病临床医学研究中心,南京210016

出　　处：《肾脏病与透析肾移植杂志》2024年第2期165-170,共6页Chinese Journal of Nephrology,Dialysis & Transplantation

基　　金：东部战区总医院临床研究专项课题(22LCYY-XH7)。

摘　　要：糖尿病肾脏疾病(DKD)可经多重机制损伤肾小球足细胞,足细胞病变进一步促进DKD进展。盐皮质激素通过作用于盐皮质激素受体(MR)调节人体水盐平衡、体液容量和血压。MR表达于足细胞、内皮细胞、系膜细胞等肾小球固有细胞,其活化将影响足细胞的结构和功能,损坏滤过屏障,导致蛋白尿。糖尿病状态下MR过度活化提高足细胞内氧化应激水平,损伤细胞超微结构,抑制足细胞自噬、促进凋亡,导致蛋白尿和肾脏局部炎症,阻断MR可避免足细胞结构受损、功能障碍和数量减少,有助于修复滤过屏障。本文将综述糖尿病导致足细胞损伤的病理生理机制,MR拮抗剂(MRA)保护足细胞的基础和临床研究,为MRA治疗DKD足细胞病变、减少蛋白尿、改善肾脏预后提供理论依据。Diabetic kidney disease(DKD)induces glomerular podocytes damages in multiple pathways,and podocyte lesions promote the progression of DKD.Mineralocorticoid regulates the salt and water concentration,fluid volume,and blood pressure by acting on mineralocorticoid receptor(MR).MR expresses on intrinsic glomerular cells,such as podocytes,endothelial cells and mesangial cells.Its activation could change the structure and function of podocytes,damage the filtration barrier,and cause proteinuria.In the condition of diabetics,over-activation of MR will produce proteinuria and inflammation within kidney locally by upreglating oxidative stress,impairing ultrastructure,inhibiting autophagy and promoting apoptosis of podocytes.Blocking MR will prevent structural impairment,dysfunction and loss of podocytes,and even repair the filtration barrier.Here we review the pathophysiological mechanism of podocyte injury caused by diabetes,and the basic and clinical studies on the protection of podocytes with MR antagonist(MRA),so as to provide a theoretical basis for MRA to ameliorate podocyte injury,reduce proteinuria,and improve kidney prognosis in the population with DKD.

关 键 词：糖尿病 足细胞 盐皮质激素受体 

分 类 号：R587.2[医药卫生—内分泌] R692.9[医药卫生—内科学]