The protective roles of liraglutide on Kawasaki disease via AMPK/mTOR/NF-κB pathway

作者：Yinjuan Ding, Yongmiao Peng, Huilan Wu, Yuqing Huang, Ke Sheng, Chao Li, Maoping Chu, Weiping Ji, Xiaoling Guo · 发表于：International Immunopharmacology · 年份：2023 · DOI：10.1016/j.intimp.2023.110028 · 被引用次数：10 · 研究领域：Kawasaki Disease and Coronary Complications、Inflammasome and immune disorders、Mechanical Circulatory Support Devices

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 t...