HIF-1α对动脉粥样硬化小鼠线粒体呼吸功能的影响  

Effect of HIF-1α on Mitochondrial Respiratory Function in Atherosclerotic Mice

作　　者：坎安·吐尔逊 朱阔 杨雪 程虎[1] 吴建江[1] 王江[1] Kanan·Tuerxun;ZHU Kuo;YANG Xue(Department of Anesthesiology,The First Affiliated Hospital of Xinjiang Medical University,Xinjiang 830054,China)

机构地区：[1]新疆医科大学第一附属医院麻醉科,乌鲁木齐830054

出　　处：《医学研究杂志》2024年第6期34-39,共6页Journal of Medical Research

基　　金：国家自然科学基金资助项目(820602168)。

摘　　要：目的观察缺血后处理(ischemia postconditioning,IPostC)对动脉粥样硬化(Apoe-/-+AS)模型小鼠心肌缺血再灌注(ischemia-reperfusion,I/R)损伤的影响,研究AAV9-HIF-1α对IPostC作用的影响机制。方法将60只Apoe-/-+AS模型小鼠按照随机数字表法分为6组,即对照组(AS-sham组)、心肌缺血再灌注组(AS-I/R组)、缺血后处理组(AS-IPostC组)、AAV9-HIF-1α+缺血后处理组(AS-AAV9-HIF-1α+IPostC组)、AAV9-NC+缺血后处理组(AS-AAV9-NC+IPostC组)、AAV9-HIF-1α+HIF-1α抑制剂+缺血后处理组(AS-AAV9-HIF-1α+2ME2+IPostC组),每组各6只。建立心肌I/R模型和IPostC模型;通过尾静脉分别注射腺相关病毒-9与人巨细胞病毒启动子阴性对照(adeno-associated virus-9 with human cytomegalovirus promoter negative control,AAV9-NC)、腺相关病毒9与表达HIF-1α的人巨细胞病毒启动子(AAV9-HIF-1α)。观察心肌组织病理学变化并测定活性氧簇(reactive oxygen species,ROS)、三磷酸腺苷(adenosine triphosphate,ATP)、线粒体呼吸酶活性;Western blot法检测缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、ATP合酶亚基b(ATP synthase subunit b,ATP5F1)、腺苷酸转运(adenylate transporter,ANT)蛋白。结果与AS-sham组比较,AS-I/R组心肌组织损伤严重,ROS含量升高,ATP含量显著降低;与AS-I/R组比较,AS-IPostC组ROS含量降低,ATP含量升高,但线粒体呼吸酶活性仍然较低,而AS-AAV9-HIF-1α+IPostC组心肌损伤明显下降,线粒体呼吸功能显著好转。结论动脉粥样硬化小鼠心肌I/R损伤时,氧化应激激活致氧自由基释放、线粒体呼吸功能减弱、细胞能量减少、心肌损伤,而AAV9-HIF-1α+IPostC通过上述机制在一定程度上能增强心肌线粒体呼吸功能。Objective To observe the effect of ischemia postconditioning(IPostC)on myocardial ischemia-reperfusion(I/R)injury in atherosclerosis(Apoe-/-+AS)model mice,and to study the mechanism of the effect of AAV9-HIF-1αon IPostC.Methods Sixty Apoe-/-+AS model mice were randomly divided into 6groups:control group(AS-sham group),Apoe-/-+AS-myocardial ischemia-reperfusion group(AS-I/R group),Apoe-/-+AS-ischemia postconditioning group(AS-IPostC group),Apoe-/-+AS-AAV9-HIF-1α+ischemia postconditioning group(AS-AAV9-HIF-1α+IPostC group),Apoe-/-+AS-AAV9-NC+ischemia postconditioning group(AS-AAV9-NC+IPostC group),Apoe-/-+AS-AAV9-HIF-1α+HIF-1αinhibitor+ischemia postconditioning group(AS-AAV9-HIF-1α+2ME2+IPostC group),6mice in each group.Establish myocardial I/R models and IPostC models;adeno-associated virus-9 with human cytomegalovirus promoter negative control(AAV9-NC)and adeno-associated virus-9 with human cytomegalovirus promoter expressing HIF-1α(AAV9-HIF-1α)was separately injected through the tail vein.The histopathological changes of myocardium was observed,reactive oxygen species(ROS),adenosine triphosphate(ATP),and the activities of mitochondrial respiratory enzyme were detected;hypoxia inducible factor-1α(HIF-1α),ATP synthase subunit b(ATP5F1),adenylate transporter(ANT)were detected by Western blot assay.Results Compared with AS-sham group,myocardial tissue injury was serious,ROS content was increased,ATP content was significantly decreased in AS-I/R group;compared with the AS-I/R group,ROS content was decreased,ATP content was increased in the AS-IPostC group,but mitochondrial respiratory enzyme activity was still lower,while myocardial injury was significantly decreased in the AS-AAV9-HIF-1α+IPostC group,and mitochondrial respiratory function was significantly improved.Conclusion During myocardial I/R injury in atherosclerotic mice,oxygen free radical activated by oxidative stress was released,mitochondrial respiratory function was weakened,cell energy was decreased,and myocardial cell was damaged,while AAV9-

关 键 词：动脉粥样硬化 缺血后处理 线粒体呼吸功能 缺氧诱导因子-1Α 小鼠 

分 类 号：R541.4[医药卫生—心血管疾病]