七氟醚后处理改善线粒体呼吸功能减轻大鼠心肌缺血再灌注损伤的机制研究

发布时间：2018-02-28 23:13

  本文关键词： 七氟醚后处理 心肌缺血再灌注损伤 低氧诱导因子-1 线粒体呼吸功能 呼吸酶活性　出处：《新疆医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:探讨七氟醚后处理是否通过调控缺氧诱导因子-1α(HIF-1α)来改善线粒体呼吸功能及呼吸酶活性减轻心肌缺血再灌注损伤。方法:88只SD大鼠(SPF级健康雄性)采用Langendorff离体心脏灌流装置建立大鼠心肌缺血再灌模型,随机分为4组(n=22):正常对照组(C)、缺血再灌注组(I/R)、七氟醚后处理组(SpostC)、MSP组【缺血再灌注组(I/R)+HIF-1α阻断剂(2-Methoxyestradiol,2ME2)+七氟醚后处理组(SpostC):(I/R+2ME2+SpostC)】。C组:持续灌注Krebs-Henseleit(K-H)液180min;I/R组平衡20min,然后灌注4℃Thomas停跳液,32℃下全心缺血40min后灌注K-H液120min;SpostC组:平衡20min后灌注4℃Thomas停跳液,32℃下全心缺血40min后灌注1.0 MAC七氟醚饱和的K-H液15min,后继续灌注正常K-H液105min;MSP组全心缺血40min后灌注含2ME2(2uM)+1.0 MAC七氟醚饱和的K-H液15min后继续灌注正常K-H液105min。记录各组平衡末(T1)及复灌末(T2)的血流动力学参数;用汉莎氧电极测定心肌线粒体3态呼吸(State3)、呼吸控制比(Respiratory Control Ratio,RCR)及烟酰胺腺嘌呤二核苷酸氧化酶(NADHO)、琥珀酸氧化酶(SucO)、细胞色素C氧化酶(CcO)等酶活性变化;用透射电镜观察心肌细胞超微结构的变化;利用荧光光度法检测心肌线粒体的活性氧(ROS)产生率;Western blot法检测HIF-1α蛋白表达水平。结果:与缺血再灌注(I/R)组相比,SpostC组的HIF-1α表达明显上调,心功能指标、线粒体3态呼吸、呼吸控制比(RCR)、细胞色素C氧化酶(CcO)、NADH氧化酶(NADHO)、琥珀酸氧化酶(SUCO)的活性、线粒体活性氧产生率明显优于I/R组,但这种优势被HIF-1α特异性抑制剂2ME2完全逆转(P0.05)。结论:七氟醚后处理通过上调HIF-1α的表达改善粒体呼吸功能及呼吸酶的活性减轻大鼠心肌缺血再灌注损伤。
[Abstract]:Objective: to investigate whether sevoflurane post-treatment can improve mitochondrial respiratory function and respiratory enzyme activity by regulating hypoxia inducible factor-1 伪 (HIF-1 伪) to reduce myocardial ischemia-reperfusion injury. Methods: Langendorff dissociation was used in 88 healthy male SD rats. Rat model of myocardial ischemia-reperfusion was established by perfusion device in vivo. The rats were randomly divided into 4 groups: normal control group, ischemia reperfusion group, sevoflurane post-treatment group, SpostCfU group [I / R) HIF-1 伪 blocker 2-Methoxyestradiolol 2ME2ME2ME2ME2)] .C group: continuous perfusion of Ks-rebHeneite K-H) 180 min-IR-IR solution for 20 mins, and then perfusion of 4 groups for 4 min after sevoflurane treatment (SpostCow-r-IR 2ME2SpostC)] .C group: continuous perfusion of Ks-rebHeneititt-K-Har solution for 20 mins. Thomas cardioplegia at 32 鈩，

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