盐皮质激素受体拮抗剂非奈利酮在2型糖尿病肾病中的作用:从分子结构到心肾保护作用机制

Mineralocorticoid receptor antagonist finerenone in DKD: From molecular structure to the cardio-renal protective mechanism

盐皮质激素受体(mineralocorticoid receptor, MR)过度激活通过介导促炎、促纤维化作用, 在糖尿病肾病(diabetic kidney disease, DKD)的发生与进展中发挥重要作用, 也是DKD治疗的重要靶点。非奈利酮(finerenone)是第三代高选择性、新型口服非甾体盐皮质激素受体拮抗剂(mineralocorticoid receptor antagonist, MRA), 通过抗炎、抗纤维化、改善免疫炎症环境等作用阻断MR过度激活, 显著降低2型糖尿病合并慢性肾脏疾病(chronic kidney disease, CKD)患者的心血管、肾脏复合终点事件发生风险, 改善心肾结局。基于其独特的分子结构, 与第一、第二代MRA相比, 非奈利酮的药物不良反应发生率更低。本文阐述了MR的分子结构及病理生理作用, 并探讨非奈利酮拮抗MR带来心肾获益作用的分子机制, 从分子结构角度探讨非奈利酮与第一、第二代MRA的优势与安全性, 为临床应用提供证据。

Mineralocorticoid receptor(MR)overactivation plays an important role in the development and progression of diabetic kidney disease(DKD)by mediating pro-inflammatory and pro-fibrotic processes,making it a key therapeutic target for DKD.Finerenone,a third-generation,highly selective,novel nonsteroidal mineralocorticoid receptor antagonist(MRA),mitigates MR overactivation through anti-inflammatory and anti-fibrotic effects and by improving the immune-inflammatory environment.This significantly reduces cardiovascular and renal composite endpoints in patients with type 2 diabetes mellitus(T2DM)and chronic kidney disease(CKD),and improve cardiorenal outcomes.Based on its novel molecular structure,Finerenone exhibits a lower incidence of adverse effects compared to the previous MRAs.This article elucidates the molecular structure and pathophysiological role of MR,and explores the molecular mechanisms through which finerenone provides cardiorenal benefits.It also discusses the advantages and safety of finerenone compared to first-and second-generation MRAs from a molecular structure perspective,providing evidence for its clinical application.