Germacrone ameliorates acute lung injury induced by intestinal ischemia-reperfusion by regulating macrophage M1 polarization and mitochondrial defects  

作　　者：Yunguang Wang Xinxin He Hua Zhang Wei Hu 

机构地区：[1]Department of Nephrology,the First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine),Hangzhou 310006,China [2]School of Clinical Medicine,Hangzhou Medical College,Hangzhou 311399,China [3]Department of Critical Care Medicine,Affiliated Hangzhou First People’s Hospital,West Lake University School of Medicine,Hangzhou 310006,China

出　　处：《Acta Biochimica et Biophysica Sinica》2025年第2期261-273,共13页生物化学与生物物理学报(英文版)

基　　金：supported by the grants from the Huadong Medicine Joint Funds of the Zhejiang Provincial Natural Science Foundation of China(No.LHDMY24H270002);the Zhejiang Provincial Medical and Health Technology Project(No.2023KY158);the Cultivation Program for Excellent Young Talents of Hangzhou First People’s Hospital(No.YQNYC202131);the Hangzhou Health Science and Technology Plan-Major Project(No.Z20220026).

摘　　要：Intestinal ischemia-reperfusion(I/R)injury severely affects the lungs.Germacrone(Ger)possesses anti-inflammatory and antioxidant properties.However,it is unclear whether it protects the lungs from I/R injury.In this study,we elucidate the mechanisms by which Ger protects lungs from I/R injury.C57BLKS/J male mice are subjected to I/R injury via complete clamping of the superior mesenteric artery.Ger is administered before intestinal I/R.Mitochondrial morphology is observed via electron microscopy.The histopathology of the lung tissues is monitored via hematoxylin-eosin and immunofluorescence staining.The mitochondrial oxygen consumption rate is measured via an XF96 extracellular flux analyzer.In the I/R mouse model,lung specimens present significant lung damage accompanied by increases in the levels of collagen III,vimentin,andα-SMA in lung tissues.After treatment with Ger,lung impairment and fibrosis in I/R-induced acute lung injury(ALI)model mice are restored,suggesting that Ger improves I/R-ALI.In addition,Ger administration decreases the release of inflammatory factors such as IL-1β,IL-6,and COX2,as well as the expressions of M1 macrophage markers,facilitating cell survival in the I/R-ALI model.Additionally,Ger(EC50:47.16μM)ameliorates mitochondrial dysfunction by increasing I/R-ALI-induced apoptosis,increasing the expression of SIRT1,and reducing the levels of HIF1-α,Nrf2,and OGG1 in MLE-12 cells.Ger may affect macrophage polarization and improve subsequent mitochondrial defects through the SIRT1-HIF1α-Nrf2 signaling pathway in MLE-12 cells,which ultimately improves lung function and lung inflammation in the I/R-ALI model.

关 键 词：lung injury GERMACRONE macrophage polarization mitochondrial function intestinal ischemia-reperfusion 

分 类 号：R73[医药卫生—肿瘤]