胰高血糖素样肽-1受体激动剂治疗射血分数保留型心力衰竭的作用机制研究进展  

Research progress on action mechanism of glucagon-like petide-1 receptor agonists in the treatment of heart failure with preserved ejection fraction

作　　者：周金鸿 高燕 ZHOU Jinhong;GAO Yan(Jinzhou Medical University Graduate Training Base,the 960th Hospital of People’s Liberation Army Joint Logistics Support Force,Liaoning Province,Jinzhou121000,China;Department of General Medicine,the 960th Hospital of People’s Liberation Army Joint Logistics Support Force,Shandong Province,Jinan250031,China)

机构地区：[1]锦州医科大学中国人民解放军联勤保障部队第九六〇医院研究生培养基地,辽宁锦州121000 [2]中国人民解放军联勤保障部队第九六〇医院全科医学科,山东济南250031

出　　处：《中国医药导报》2024年第35期55-59,64,共6页China Medical Herald

基　　金：军队后勤科研项目保健专项课题(23BJZ45)。

摘　　要：射血分数保留型心力衰竭(HFpEF)是一种异质性疾病,不同表型间预后差别较大,药物治疗也不同于射血分数降低型心力衰竭,而胰高血糖素样肽(GLP)-1受体激动剂在HFpEF中的应用为该领域带来曙光。本文从以下几个方面探讨GLP-1受体激动剂治疗HFpEF的作用机制:改善系统性炎症;调节脂肪代谢,减少内脏脂肪含量及心外膜脂肪组织厚度,改善胰岛素敏感性,并减轻体重;通过PKA/RhoA/ROCK信号通路减轻心脏代谢失调,预防心脏肥大;升高血管舒张剂水平,刺激心房利尿钠肽分泌,扩张外周血管,减少皮质血管紧张素Ⅱ分泌,抑制血管平滑肌细胞增殖和迁移使血管舒张,多重机制发挥降压作用。调节血脂、改善血糖代谢,并通过改善肾血流动力学和肾小球滤过率发挥肾脏保护作用,为HFpEF的治疗提供参考依据。Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous disease,with a significantly different prognosis among different phenotypes,and drug treatment is also different from that of heart failure with reduced ejection fraction.The application of glucagon-like petide(GLP)-1 receptor agonists in HFpEF brings new light to this field.This article explores action mechanism of GLP-1 receptor agonists in the treatment of HFpEF from the following aspects:improve systemic inflammation;regulate fat metabolism,reduce visceral fat content,and epicardial fat tissue thickness,improve insulin sensitivity,and reduce body weight;alleviate cardiometabolic disorders,and prevent cardiac hypertrophy through PKA/RhoA/ROCK signaling pathway;increase the level of vasodilators,stimulate atrial natriuretic peptide secretion,dilate peripheral blood vessels,reduce cortical angiotensinⅡsecretion,inhibit proliferation and migration of vascular smooth muscle cells leads to vasodilation,and multiple mechanisms play a role in blood pressure reduction.Regulate blood lipids,improve blood glucose metabolism,and play a role in kidney protection by improving renal hemodynamics,and glomerular filtration rate,providing a reference for the treatment of HFpEF.

关 键 词：胰高血糖素样肽-1受体激动剂 射血分数保留型心力衰竭 心外膜脂肪组织 

分 类 号：R541.6[医药卫生—心血管疾病]