川崎病（KD）是一种在儿童中发生的急性发热性皮疹疾病，其病因尚不明确且伴有冠状动脉损伤。本研究的主要目的是研究利拉鲁肽对KD的保护作用，并阐明其作用机制。使用酵母菌溶解物水溶性分馏物（CAWS）诱导的小鼠KD模型以及体外人脐静脉内皮细胞（HUVEC）模型，研究利拉鲁肽对KD的抗炎和抗凋亡作用。体内结果显示，利拉鲁肽可以显著减轻KD小鼠的冠状动脉损伤，这表现为冠状动脉周围炎症浸润的减少，炎症细胞因子和趋化因子表达的下调，TUNEL（末端脱氧核苷酸转移酶dUTP尼克末端标记法）阳性细胞率的降低。体外结果也显示，利拉鲁肽可以通过下调炎症和趋化因子指标的表达显著缓解TNF-α诱导的HUVECs炎症，并通过减少细胞凋亡比例，降低线粒体膜电位（△Ψm），降低细胞内反应性氧种水平（ROS）以及增加BCL-2/BAX比值，抑制TNF-α诱导的HUVEC凋亡。进一步的体内外研究表明，利拉鲁肽可以通过AMPK/mTOR/NF-κB途径拯救内皮细胞损伤。总之，利拉鲁肽可以通过激活AMPK/mTOR/NF-κB途径抑制内皮细胞的炎症和凋亡，从而发挥对KD的保护作用。 版权所有©2023 Elsevier B.V.，由作者发表。

Kawasaki disease (KD) is an acute febrile rash illness among children of unknown etiology, with coronary artery injury. The main purpose of this study was to investigate the protective effects of liraglutide on KD, and elucidate the underlying mechanisms. The candida albicans water-soluble fraction (CAWS)-induced coronary arteritis of mouse KD model in vivo and tumor necrosis factor α (TNF-α) induced endothelial cell injury of human umbilical vein endothelial cell (HUVEC) model in vitro were used to explore the anti-inflammation and anti-apoptosis effects of liraglutide on KD. In vivo results showed that liraglutide could significantly alleviate the coronary artery injury of KD mice, as evidenced by the reduction of inflammatory infiltration around the coronary arteries, downregulation of inflammatory cytokines and chemokines expressions, and decrease of TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) positive cell rates. The results in vitro also displayed that liraglutide could markedly relieve the inflammatory of TNF-α induced HUVECs through downregulating the expressions of inflammatory and chemokine indicators as well as inhibit TNF-α induced HUVEC apoptosis by the less ratio of apoptotic cells, the more loss of mitochondrial membrane potential (△Ψm), the lower level of intracellular reactive oxygen species (ROS), and the more ratio of BCL-2/BAX. Further in vivo and in vitro studies demonstrated that liraglutide could rescue endothelial cell injury through AMPK/mTOR/NF-κB pathway. In conclusion, liraglutide could play protective roles on KD through inhibiting endothelial cell inflammation and apoptosis via the activation of AMPK/mTOR/NF-κB pathway.Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.