阿片受体介导缺血后处理的心肌保护作用及其受体后机制

发布时间：2018-07-06 10:10

本文选题：心脏 + 缺血后处理　；参考：《浙江大学》2006年硕士论文

【摘要】：背景: 20世纪80年代中期,Murry等首次提出心肌在经受多次短暂缺血复灌后能在随后的长时间缺血中延迟并减轻心肌损伤,即缺血预处理(ischemic preconditioning,IP)的心肌保护作用。但由于这种预处理需在缺血前施与,而在临床实践中,患者往往在出现严重缺血导致心肌梗塞后就诊,使其临床应用价值受限。2003年Vinten-Johansen实验室首次提出了缺血后处理的概念。缺血后处理是指在心肌长时间缺血后,于复灌初期立即给予心肌反复多次的短暂的复灌/停灌,具有明显的对抗心脏缺血/复灌损伤的保护作用。但缺血后处理的心肌保护作用机制尚未完全清楚。研究表明,心脏阿片受体参与缺血预处理的心肌保护作用。根据阿片的生物学与药理学特性,可分为三种受体,分别为Mu(μ)、Kappa(κ)及Delta(δ)三种类型。对成年大鼠心室肌组织的功能性和转录水平的研究都表明心室仅有δ和κ阿片受体,而无μ阿片受体。这些受体的激活可产生急性和慢性心脏保护作用,其中涉及的信号途径包括Gi/o蛋白、蛋白激酶C、酪氨酸激酶、丝裂原活化蛋白激酶和ATP敏感性钾通道等。研究证实,阿片受体的激活导致了线粒体钙激活钾通道(mitochondrial calcium activated potassium channel,mKCa)通道开放而发挥心肌保护作用。mKCa通道是心肌线粒体膜上存在的通道,已知它的开放是心肌缺血预处理保护作用的触发机制之一。因此,我们假设阿片受体和mKCa通道的开放可能均参予缺血后处理的心肌保护作用。本实验旨在探讨缺血后处理与缺血预处理联合在严重缺血心脏损伤中的作用,mKCa通道和阿片受体是否参予心肌的缺血后处理的保护作用。
[Abstract]:Background: in the mid-1980s, Murry et al first proposed that myocardial injury can be delayed and alleviated during subsequent long periods of ischemia after several short periods of ischemia and reperfusion. This is the myocardial protective effect of ischemic preconditioning IP. However, because this kind of preconditioning needs to be applied before ischemia, and in clinical practice, patients often go to hospital after myocardial infarction due to severe ischemia, which limits the clinical application value. In 2003, Vinten-Johansen laboratory first put forward the concept of ischemic post-processing. Post-ischemic treatment is a kind of protection against myocardial ischemia / reperfusion injury, which is given immediately after a long period of ischemia and immediately after reperfusion for several times. However, the mechanism of myocardial protection after ischemic treatment has not been fully understood. Studies have shown that cardiac opioid receptors participate in the myocardial protection of ischemic preconditioning. According to the biological and pharmacological characteristics of opioids, they can be divided into three types: mu (渭) Kappa (魏) and Delta (未). The functional and transcriptional levels of ventricular myocytes in adult rats showed that there were only 未 and 魏 opioid receptors, but no 渭 opioid receptors in the ventricle. The activation of these receptors can produce acute and chronic cardioprotective effects. The signal pathways involved include Giro protein, protein kinase C, tyrosine kinase, mitogen-activated protein kinase and ATP-sensitive potassium channel. It has been demonstrated that the activation of opioid receptors leads to the opening of mitochondrial calcium activated potassium channel (mitochondrial calcium activated potassium channel mKCa) channel, which may play a role in myocardial protection. Its opening is known to be one of the trigger mechanisms of myocardial ischemic preconditioning. Therefore, we hypothesized that the opening of opioid receptor and mKCa channel may be involved in myocardial protection after ischemia. The purpose of this study was to investigate the role of combination of ischemic postconditioning and ischemic preconditioning in the pathogenesis of severe ischemic heart injury and the role of mKCa channel and opioid receptor in the protection of myocardial ischemic postconditioning.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R363

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