外源性一氧化碳释放分子CORM-2对大鼠离体心脏缺血复灌的保护作用及其作用机制的研究

发布时间：2018-11-03 14:35

【摘要】：背景和目的临床上当急性心肌梗塞发生的时，常立即用血管成形术来进行治疗，以减少心肌损伤。但是此疗法在让缺血的心脏恢复血氧需求时却诱导了缺血复灌(I／R)损伤。氧化应激是缺血复灌损伤主要原因。过去曾一直被认为是破坏细胞呼吸作用的有害物质的一氧化碳，目前的研究指出，一氧化碳(CO)是一个重要的信号分子，它能在损伤诱导的各种机体应激中起保护组织的作用。事实上CO现在已经被认为是一种通用信号分子在心血管、神经和免疫的生理和病理过程中都起着重要的调节作用。作为气体信号分子的CO在机体内由血红素加氧酶(HO)催化血红素产生，内源性CO被认为能抑制血管平滑肌细胞增生，抑制心脏移植的免疫排斥等。而这种内源性CO的药理学效应已经证明能被外源性CO取代。而目前研究指出一些特定的过渡金属羰基化合物诸如一氧化碳释放分子(CORMs)之类能在合适的条件下分解释放出CO，这为临床治疗提供了方便。此外，CO精确的组织保护作用的机制还不清楚。在本研究中，我们通过使用CORM—2研究是否外源性CO对离体心脏缺血复灌损伤有保护作用及其有效浓度范围，并且研究了CO的作用机制。方法采用Langendoff离体心脏灌流模型，用结扎心脏冠脉前降支30min造成心肌缺血，，松开结扎120min作为再灌。观察心脏收缩功能，心肌酶学和心肌梗死面积等指标。
[Abstract]:Background and objective when acute myocardial infarction occurs, angioplasty is often used immediately to reduce myocardial injury. But the treatment induces ischemia-reperfusion (I-R) damage by restoring blood oxygen demand to the ischemic heart. Oxidative stress is the main cause of ischemia reperfusion injury. Carbon monoxide, once thought to be a harmful substance that disrupts cell respiration, has been shown to be an important signaling molecule in recent studies. It can protect tissues in various kinds of stress induced by injury. In fact, CO is now considered to be a common signaling molecule that plays an important regulatory role in the physiological and pathological processes of the cardiovascular, nerve and immune systems. CO, as a gas signaling molecule, is produced by heme oxygenase (HO) in vivo. Endogenous CO is thought to inhibit the proliferation of vascular smooth muscle cells and the immune rejection of heart transplantation. The pharmacological effects of this endogenous CO have been shown to be substituted by exogenous CO. Some specific transition metal carbonyl compounds, such as carbon monoxide releasing molecule (CORMs), can decompose and release CO, under suitable conditions, which is convenient for clinical treatment. In addition, the precise mechanism of CO's tissue protection is unclear. In this study, we used CORM-2 to study whether exogenous CO could protect isolated heart from ischemia-reperfusion injury and its effective concentration range, and to study the mechanism of CO. Methods Langendoff isolated heart perfusion model was used. Myocardial ischemia was induced by ligation of anterior descending coronary artery 30min and 120min was released and ligated as reperfusion. Cardiac systolic function, myocardial enzymology and myocardial infarction size were observed.
【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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