Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1αpathway

作     者：Dongmei Zhu Lingli Luo Hanjie Zeng Zheng Zhang Min Huang Suming Zhou 

作者机构：Department of Geriatrics Intensive Care Unitthe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 

出 版 物：《The Journal of Biomedical Research》 (生物医学研究杂志（英文版）)

年 卷 期：2023年第37卷第4期

页      面：290-301页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：supported by grants from the National Natural Science Youth Foundation of China(Grant No.81501201) the National Natural Science Youth Foundation of Jiangsu Province(Grant No.BK20151032) Min Huang,and the project of Critical Care Medicine of the Key Clinical Specialty of Jiangsu Province 

主　　题：11β-HSD1 LPS sepsis-induced myocardial dysfunction inflammation oxidative stress 

摘      要：Sepsis-induced myocardial dysfunction is primarily accompanied by severe sepsis,which is associated with high morbidity and mortality.11β-hydroxysteroid dehydrogenase type 1(11β-HSD1),encoded by Hsd11b1,is a reductase that can convert inactive cortisone into metabolically active cortisol,but the role of 11β-HSD1 in sepsis-induced myocardial dysfunction remains poorly *** current study aimed to investigate the effects of 11β-HSD1 on a lipopolysaccharide(LPS)-induced mouse model,in which LPS(10 mg/kg)was administered to wild-type C57BL/6J mice and 11β-HSD1 global knockout *** asscessed cardiac function by echocardiography,performed transmission electron microscopy and immunohistochemical staining to analyze myocardial mitochondrial injury and histological changes,and determined the levels of reactive oxygen species and biomarkers of oxidative *** also employed polymerase chain reaction analysis,Western blotting,and immunofluorescent staining to determine the expression of related genes and *** investigate the role of 11β-HSD1 in sepsis-induced myocardial dysfunction,we used LPS to induce lentivirus-infected neonatal rat ventricular *** found that knockdown of 11β-HSD1 alleviated LPS-induced myocardial mitochondrial injury,oxidative stress,and inflammation,along with an improved myocardial function;furthermore,the depletion of 11β-HSD1 promoted the phosphorylation of adenosine 5′-monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor gamma coactivator 1α(PGC-1α),and silent information regulator 1(SIRT1)protein levels both in vivo and in ***,the suppression of 11β-HSD1 may be a viable strategy to improve cardiac function against endotoxemia challenges.