南方医科大学学报2024，Vol.44Issue(3)：507-514,8.DOI:10.12122/j.issn.1673-4254.2024.03.12
HTD4010可减轻脓毒症心肌病小鼠的心肌损伤:基于促进AMPK/mTOR信号通路介导的自噬
HTD4010 attenuates myocardial injury in mice with septic cardiomyopathy by promoting autophagy via the AMPK/mTOR signaling pathway
摘要
Abstract
Objective To investigate the protective effects of HTD4010 against lipopolysaccharide(LPS)-induced septic cardiomyopathy(SCM)in mice and explore the mechanisms mediating its effect.Methods Forty-five male ICR mice were randomized equally into control group,LPS(10 mg/kg)group,and LPS+HTD4010 group(in which 2.5 mg/kg HTD4010 was injected subcutaneously at 1 h and 6 h after LPS injection).Cardiac function of the mice was evaluated by ultrasound,and pathological changes in the myocardial tissues were observed with HE staining.The levels of IL-6 and TNF-α in serum and myocardial tissues were detected using ELISA,and apoptosis of the cardiomyocytes was detected with TUNEL staining.The expression levels of the key proteins associated with apoptosis,autophagy and the AMPK/mTOR pathway in the myocardial tissues were detected using Western blotting.The ultrastructural changes of cardiac myocardial mitochondria was observed with transmission electron microscopy.Results LPS exposure caused severe myocardial damage in mice,characterized by myocardial fiber rupture,structural disorder,inflammatory cell infiltration,and mitochondrial damage.The LPS-treated mice exhibited significantly decreased cardiac LVEF and FS values,elevated IL-6 and TNF-αlevels in serum and myocardial tissue,and an increased myocardial cell apoptosis rate with enhanced expressions of Bax,p-62 and p-mTOR and lowered expressions of Bcl-2,LC3 Ⅱ/I,Beclin-1 and p-AMPK(P<0.05 or 0.01).Treatment of the septic mice with HTD4010 significantly alleviated myocardial damage,increased LVEF and FS values,reduced IL-6 and TNF-α levels in serum and myocardial tissue,decreased cardiomyocyte apoptosis,lowered myocardial expressions of Bax,p-62 and p-mTOR,and increased Bcl-2,LC3 Ⅱ/I,Beclin-1 and p-AMPK expressions(P<0.05 or 0.01).Conclusion HTD4010 can attenuate myocardial injury in SCM mice possibly by promoting autophagy via modulating the AMPK/mTOR signaling pathway.关键词
脓毒症心肌病/HTD4010/AMPK/mTOR/自噬Key words
septic cardiomyopathy/HTD4010/AMPK/mTOR/autophagy引用本文复制引用
肖红敏,韩保松,郭家成,吴超,吴敬医..HTD4010可减轻脓毒症心肌病小鼠的心肌损伤:基于促进AMPK/mTOR信号通路介导的自噬[J].南方医科大学学报,2024,44(3):507-514,8.基金项目
安徽省高校自然科学研究重点项目(KJ2020A0616) （KJ2020A0616）
安徽省教育厅新时代育人质量工程项目(研究生教育2022zyxwjxalk155) （研究生教育2022zyxwjxalk155）
芜湖市科技计划项目(2020ms3-5) （2020ms3-5）
皖南医学院教学质量与教学改革工程项目(2021ylkc17) （2021ylkc17）
皖南医学院横向科研项目(H202303) （H202303）
