Propofol postconditioning ameliorates hypoxia/reoxygenation induced H9c2 cell apoptosis and autophagy via upregulating forkhead transcription factors under hyperglycemia  

作　　者：Rong-Hui Han He-Meng Huang Hong Han Hao Chen Fei Zeng Xiang Xie Dan-Yong Liu Yin Cai Liang-Qing Zhang Xin Liu Zheng-Yuan Xia Jing Tang 

机构地区：[1]Department of Anesthesiology,Affiliated Hospital of Guangdong Medical University,Guangdong,57 South Renming Avenue Xiashan District,Zhanjiang City,524000,Guandong Province,China [2]Department of Emergency,Affiliated Hospital of Guangdong Medical University,Zhanjiang,524000,China [3]Department of Anesthesiology,the Eighth Affiliated Hospital,Sun Yat-Sen University,Guangzhou,518000,China [4]Department of Anesthesiology,Guangzhou First People’s Hospital,The Second Affiliated Hospital of South China University of Technology,Guangzhou,510000,China [5]Department of Anesthesiology,The Second Affiliated Hospital and Yuying Children’s Hospital,Wenzhou Medical University,Wenzhou,325000,China [6]Department of Health Technology and Informatics,The Hong Kong Polytechnic University,Hung Hom,999077,Hong Kong SAR,China [7]State Key Laboratory of Pharmaceutical Biotechnology,Department of Medicine,The University of Hong Kong,Pok Fu Lam,999077,Hong Kong SAR,China

出　　处：《Military Medical Research》2022年第3期286-302,共17页军事医学研究（英文版）

基　　金：supported by the National Natural Science Foundation of China grant (NSFC81970247)。

摘　　要：Background:Administration of propofol,an intravenous anesthetic with antioxidant property,immediately at the onset of post-ischemic reperfusion(propofol postconditioning,P-PostC) has been shown to confer cardioprotection against ischemia–reperfusion(I/R) injury,while the underlying mechanism remains incompletely understood.The forkhead box O(FoxO) transcription factors are reported to play critical roles in activating cardiomyocyte survival signaling throughout the process of cellular injuries induced by oxidative stress and are also involved in hypoxic postconditioning mediated neuroprotection,however,the role of FoxO in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown.Methods:Rat heart-derived H9c2 cells were exposed to high glucose(HG) for 48 h,then subjected to hypoxia/reoxygenation(H/R,composed of 8 h of hypoxia followed by 12 h of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol(P-PostC) at the onset of reoxygenation.After having identified the optical concentration of propofol,H9c2 cells were subjected to H/R and P-PostC in the absence or presence of FoxO1 or FoxO3a gene silencing to explore their roles in P-PostC mediated protection against apoptotic and autophagic cell deaths under hyperglycemia.Results:The results showed that HG with or without H/R decreased cell viability,increased lactate dehydrogenase(LDH) leakage and the production of reactive oxygen species(ROS) in H9c2 cells,all of which were significantly reversed by propofol(P-PostC),especially at the concentration of 25 μmol/L(P25)(P<0.05,NC vs.HG;HG vs.HG+HR;HG+HR+P12.5 or HG+HR+P25 or HG+HR+P50 vs.HG+HR).Moreover,we found that propofol(P25) decreased H9c2 cells apoptosis and autophagy that were concomitant with increased FoxO1 and FoxO3a expression(P<0.05,HG+HR+P25 vs.HG+HR).The protective effects of propofol(P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a(P<0.05,HG+HR+P25 vs.HG+HR+P25+siRNA-1 or HG+HR+P25+siRNA-5

关 键 词：Hypoxia/reoxygenation injury HYPERGLYCEMIA High glucose Propofol postconditioning Apoptosis AUTOPHAGY Forkhead box O 

分 类 号：R614[医药卫生—麻醉学]