心肌保护中电耦联特性的改变及其机制研究

发布时间：2018-05-26 01:09

本文选题：心肌 + 保护　；参考：《浙江大学》2005年博士论文

【摘要】：缺血预处理(ischemic preconditioning,IPC)是一种强有力的内源性心肌保护干预,被众多研究者所关注。已经发现腺苷、乙酰胆碱、儿茶酚胺以及阿片肽类等物质以及相关受体参与了IPC的心肌保护作用,但IPC如何介导保护的机理目前尚未明了。最近研究发现,IPC的心肌保护作用与缝隙连接密切相关,IPC具有使心肌在缺血期间电脱耦联延迟作用,这具有很重要的意义,因为电脱耦联的出现是心肌不可逆损伤开始的标志。但其它心肌保护措施或处理机制中是否也存在类似的电耦联特性的改变,尚未见报道。我们认为,心肌细胞间的电耦联是心脏电生理学特性的基本元素,也是心肌细胞在遭受各种应激后对抗损伤的关键机制,因此,我们推测,心肌电耦联也很可能是各种心肌保护措施和药物的作用靶点。本课题将应用缝隙连接脱耦联剂heptanol、非特异阿片受体激动剂morphine和κ-阿片受体特异激动剂U50,488H三种不同处理诱导心肌保护作用,观察这三种具有不同特点的处理诱导的心肌保护中电耦联特性的变化,发现心肌保护的一般规律,并探讨心肌保护中电耦联特性变化的内在机制。目的 1.使用缝隙连接脱耦联剂heptanol分别在离体心脏水平和整体心脏水平缺血/复灌前进行预处理,观察heptanol对离体心脏或整体心脏缺血/复灌损伤所致的心律失常和梗死面
[Abstract]:Ischemic preconditioning (IPC) is a powerful endogenous myocardial protection intervention, which has been concerned by many researchers. Adenosine, acetylcholine, catecholamine, opioid peptides and related receptors have been found to be involved in the myocardial protection of IPC, but the mechanism of IPC mediated protection is not clear. Recently, it has been found that the myocardial protective effect of IPC is closely related to the gap junction. IPC has the effect of delaying the electrical decoupling of myocardium during ischemia, which is of great significance, because the appearance of electrical decoupling is a sign of the beginning of irreversible myocardial injury. However, it has not been reported whether there is a similar change in electrocoupler characteristics in other myocardial protective measures or mechanisms. We believe that electrical coupling between cardiomyocytes is a fundamental element of cardiac electrophysiology and a key mechanism for cardiomyocytes to resist damage after various stresses, so we conjecture, Electrocardial coupling is also likely to be the target of various myocardial protection measures and drugs. In this study, we used gap junction decoupling agent heptanol, non-specific opioid receptor agonist morphine and 魏 -opioid receptor specific agonist U50488H to induce myocardial protection. The changes of electrical coupling characteristics in myocardial protection induced by these three different treatments were observed, the general laws of myocardial protection were found, and the internal mechanism of the changes of electrical coupling characteristics in myocardial protection was discussed. Purpose 1. The gap junction decoupling agent (heptanol) was used to pretreat the arrhythmias and infarct surfaces of isolated heart and global heart before ischemia / reperfusion, respectively. The effects of heptanol on arrhythmias and infarct surface of isolated heart or whole heart were observed.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R33

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