缺氧诱导因子-1/自噬在硫化氢预处理大鼠心肌缺血再灌注损伤中的作用与机制研究  

Effects and action mechanism of hypoxia-inducible factor-1/autophagy in hydrogen sulfide preconditioning in myocardial ischemia-reperfusion injury in rats

作　　者：毛忠文[1] 邓秋芳 李静[1] 王新云[3] 甘金城 骆福秀[1] MAO Zhongwen;DENG Qiufang;LI Jing(Department of Emergency,Nanxishan Hospital,Guangxi,Guilin 541002,China;不详)

机构地区：[1]广西壮族自治区南溪山医院急诊科,广西壮族自治区桂林市541002 [2]广西壮族自治区南溪山医院科研科,广西壮族自治区桂林市541002 [3]广西壮族自治区南溪山医院心血管内科,广西壮族自治区桂林市541002

出　　处：《河北医药》2022年第2期170-175,共6页Hebei Medical Journal

基　　金：广西壮族自治区卫生健康委员会自筹经费科研课题(编号:Z20190070)。

摘　　要：目的研究缺氧诱导因子-1/自噬在硫化氢预处理大鼠心肌缺血再灌注损伤中的作用与机制。方法选取SD健康大鼠40只,将大鼠随机分为对照组(C组)、预处理组(H组)、模型组(I/R组)、预处理组+模型组(HI组),建模前H组给予5μmol/kg的硫化氢注射于大鼠左侧肾动脉,建模型成功后,HI组给予5μmol/kg的H_(2)S与左侧肾动脉注射,C组和I/R组不作任何处理。所有大鼠在给硫化氢1周后,对大鼠SOD、MDA、T-AOC、心功能指标、心肌酶水平、心肌缺血面积、心肌梗死面积、梗死区占心室比以及心肌组织中HIF-1α、LC3Ⅰ、LC3Ⅱ、P62、Beclinl-1蛋白表达量进行检测。结果I/R组、HI组大鼠心肌组织SOD、T-AOC水平、LVESP、FS、EF、LC3Ⅰ蛋白表达量均低于C组、H组,且MDA、LVEDP、CK-MB、LDH、cTnT水平及HIF-1α、LC3Ⅱ、P62、Beclinl-1蛋白表达量均高于C组、H组,差异有统计学意义(P<0.05);HI组大鼠心肌组织SOD、T-AOC水平、LVESP、FS、EF、LC3Ⅰ蛋白表达量均高于I/R组,且MDA、LVEDP、CK-MB、LDH、cTnT水平及HIF-1α、LC3Ⅱ、P62、Beclinl-1蛋白表达量均低于I/R组,差异有统计学意义(P<0.05)。结论硫化氢对大鼠心肌缺血再灌注损伤有保护作用,能够缩小心肌梗死面积,其作用机制可能与HIF-1α/Autophagy通路有关,抑制再灌注自噬的表达,从而减轻心肌缺血再灌注损伤。Objective To investigate the effects and action mechanism of hypoxia-inducible factor-1/autophagy in hydrogen sulfide preconditioning in myocardial ischemia-reperfusion injury in rats.Methods Forty healthy SD rats(SPF grade)were randomly divided into control group(group C),preconditioning group(group H),model group(I/R group),preconditioning group+model group(HI group).Before modeling,the rats in group H were injected with 5μmol/kg of H 2S into the left renal artery of rats.After successful modeling,the rats in HI group were given 5μmol/kg of H2S and left renal artery.However the rats in group C and I/R group were not treated after intravenous injection.All the rats were given H2S for 1 week,then the levels of SOD,MDA,T-AOC,cardiac function index,myocardial enzyme level,myocardial ischemic area,myocardial infarction area,the ratio of infarcted area to ventricle and the expression levels of HIF-1α,LC3Ⅰ,LC3Ⅱ,P62,Beclinl-1 protein in myocardial tissue were detected.Results The expression levels of SOD,T-AOC,LVESP,FS,EF and LC3Ⅰin myocardial tissue of rats in I/R group and HI groups were significantly lower than those in group C and group H,and the expression levels of MDA,LVEDP,CK-MB,LDH,cTnT and HIF-1α,LC3Ⅱ,P62 and Beclinl-1 in HI group were significantly higher than those in group C and group H group(P<0.05),moreover,the levels of MDA,LVEDP,CK-MB,LDH,cTnT and the expression levels of HIF-1α,LC3Ⅱ,P62,Beclinl-1 significantly lower than those in in I/R group(P<0.05).Conclusion Hydrogen sulfide has protective effects on myocardial ischemia-reperfusion injury in rats,which can reduce the size of myocardial infarction,and its action mechanism may be related to HIF-1alpha/Autophagy pathway,which can inhibit the expression of autophagy during reperfusion,thereby alleviating myocardial ischemia-reperfusion injury.

关 键 词：缺氧诱导因子-1/自噬 硫化氢 心肌缺血再灌注损伤 

分 类 号：R542.2[医药卫生—心血管疾病]