上调HIF-1对老龄大鼠心肌线粒体功能的影响  

Effect of upregulation of HIF-1 on myocardial mitochondrial function in aged rats

作　　者：吴建江[1] 杨龙[1] 太来提·台万古 陈思宇[1] 王江[1] WU Jianjiang;YANG Long;Tailaiti Taiwangu;CHEN Siyu;WANG Jiang(Department of Anesthesiology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 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：《新疆医科大学学报》2021年第1期28-32,共5页Journal of Xinjiang Medical University

基　　金：新疆维吾尔自治区重点实验室开放课题(2017D04007)。

摘　　要：目的评价老龄大鼠心肌发生缺血再灌注(I/R)损伤时,应用氯化钴(CoCl2)上调缺氧诱导因子(HIF-1)对心肌线粒体呼吸功能的影响。方法雄性SD大鼠60只(其中健康大鼠24只、健康老龄大鼠36只)。健康SD大鼠24只(体重350~400 g)随机分为两组,每组12只:正常对照组(N组)为直接灌注180 min;正常大鼠+I/R组(I/R组)为稳定灌流30 min后,全心缺血45 min+再灌注105 min。健康老龄雄性SD大鼠36只(体重350~400 g)随机分为3组,每组12只:老龄大鼠+I/R组(A组)处理同I/R组;老龄大鼠+CoCl2组(A+CoCl2组)为稳定灌流30 min后,全心缺血45 min+再灌注105 min;老龄大鼠+CoCl2+HIF-1阻断剂组(A+CoCl2+2ME2组)为稳定灌流30 min后,全心缺血45 min+15 min 2ME2+90 min再灌注。溶于0.9%氯化钠溶液的CoCl2于心脏缺血前24 h腹腔注射30 mg/kg,HIF-1阻断剂2-Methoxyestradio(l 2ME2)(2 mol/L,复灌前15 min加入K-H液)。心肌I/R模型建立使用Langendorff离体心脏灌流装置,联合HIF-1阻断剂2ME2进行后处理,并测定各组心功能指标、线粒体结构、活性氧簇(ROS)产生率、三磷酸腺苷(ATP)含量、线粒体呼吸功能及酶活性。观察CoCl2处理对于老龄大鼠心肌线粒体各项指标的变化。结果老龄大鼠心肌发生I/R损伤,实施CoCl2处理的A+CoCl2组心功能稳定,ROS产生率降低,ATP含量增加(vs I/R组,P<0.05),并且线粒体呼吸功能改善,酶活性稳定(vs I/R组,P<0.05),但这种优势被HIF-1通路特异性阻断剂2ME2消除(vs A+CoCl2组,P<0.05)。结论老龄心肌I/R损伤模型中,CoCl2处理能增强心肌线粒体呼吸功能和呼吸酶活性。Objective To evaluate the effect of Cobalt chloride(CoCl2)up-regulating hypoxia-inducible factor(HIF-1)on mitochondrial respiratory function during myocardial ischemia-reperfusion(I/R)injury in the aged rat myocardium.Methods Twenty-four healthy SD rats(weight 350~400 g)were randomly divided into 2 groups:normal control group(N group)with normal perfusion for 180 mins,and normal rats+I/R group(I/R group)with stable normal perfusion for 30 mins,and then ischemia of whole heart for 45 mins and reperfusion for 105 mins.Thirty-six healthy aged male SD rats(weight 350~400 g)were randomly divided into 3 groups:aged rats+I/R group(A group)treated the same to the I/R group;aged rats+CoCl2 group(A+CoCl2 group)pretreated with CoCl2(30 mg/kg)in 24 hrs before ischemia,and then treated the same to the I/R group;aged rats+CoCl2+HIF-1 blocker group(A+CoCl2+2ME2 group)pretreated with CoCl2,andafter ischemia,2ME2(2 mol/L in K-H solution)perfusion for 15 mins,and then reperfusion for 90 mins.The Langendorff isolated cardiac perfusion device was used to establish a myocardial ischemia-reperfusion injury model.The changes of cardiac function index,mitochondrial structure,ROS production rate,ATP content,mitochondrial respiratory function and enzyme activity were tested.Results I/R injury occurred in the myocardium of the aged rats.The A+CoCl2 group had stable heart function,decreased reactive oxygen species(ROS)production rate,increased ATP content,and improved mitochondrial respiratory function and stable enzyme activity(vs I/R group,P<0.05),but this advantage was eliminated by the HIF-1 pathway specific blocker 2ME2(vs A+CoCl2 group,P<0.05).Conclusion In the I/R injury model of the aged rats,CoCl2 pretreatment can enhance the respiratory function and respiratory enzyme activity of myocardial mitochondria.

关 键 词：氯化钴 缺氧诱导因子 老龄心肌 心肌保护 线粒体呼吸功能 

分 类 号：R-332[医药卫生]