基因重组生长激素对心肌缺血—再灌注损伤保护作用的实验研究
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摘要
研究背景：心肌保护是心脏外科至关重要而又长研不衰的课题。以高钾为主要成份的各种心肌保护液的临床应用明显改善了体外循环手术中心肌保护效果和心脏手术成功率，但心肌缺血—再灌注损伤(myocardial ischemia-reperfusion injury MIRI)仍未得到根本解决。冠状动脉溶栓术、经皮腔内冠状动脉成形术(PTCA)、冠状动脉旁路移植术的广泛开展，也使得心肌缺血—再灌注损伤越来越受到广大基础和临床工作者的重视，成为一个亟需解决的重要问题。缺血预适应是机体产生对心肌缺血—再灌注损伤的一种内源性保护作用，尽管动物实验结果已经证明其确切的心肌保护效果，但由于伦理观念的影响在临床上很难实施。心肌缺血—再灌注损伤的发生与很多因素有关，其中最主要的就是：(1)氧自由基(OFR)的作用；(2)钙的作用：主要是钙超载；(3)内皮细胞的激活导致内皮介质释放失衡，细胞表面特性改变，产生血管收缩、白细胞粘附等效应。同时促使大量中性粒细胞(PMNs)和血小板在血管内皮表面粘附和聚集，导致微血栓形成和毛细血管堵塞，产生“无复流”现象；(4)炎症反应的作用：心肌缺血—再灌注时成熟心肌细胞合成、分泌肿瘤坏死因子(TNFα)，干扰钙的调控影响心肌兴奋—收缩耦联，进而影响心脏收缩和舒张功能，同时还干扰心肌细胞凋亡及诱导其他心肌抑制物质如IL—1、IL-2的生成。(5)中性粒细胞通过与其他细胞的相互作用介导内皮细胞和心肌细胞损伤；同时产生氧自由基和蛋白酶损伤
[Background]Myocardial protection is an extremely important subject and has been studied all through in cardiac surgical region. Application of various cardioplegia have significantly improved the myocardial protective effect and surgical results but none of them is perfect.The problem of myocardial ischemia-reperfusion injury(MIRI) is not yet resolved ultimately.With the extensive development of thrombolysis, coronary artery bypass grafting(CABG) and percutaneous transluminal coronary angioplasty(PTCA),more and more clinical and preclinical scholars attach importance to the problem of myocardial ischemia-reperfusion injury. MIRI is relevant to many kinds of factors,in which apoptosis has an extreme affinity with it.Growth hormone is a kind of peptide which includes 191 amino acid,its protection for cultured cardiomyocytes from neonatal rats and for necrotic myocardium has been reported ,However,the effects of rGH on myocardial ischemia/reperfusion and the mechanism are not yet clear, So, we designed this subject in order to seek an effective anti-apoptotic agent to attenuate the myocardial ischemia/reperfusion.
[Objective] Using the wistar rat model of myocardial ischemic-reperfusion to probe into the changes of cardiomyocyte apoptotic index and expression of its relative gene at the different timepoint after ischemic-reperfusion.At the same time ,to observe the effect of recombinant human growth hormone( rGH) on cardiomyocyte apoptosis and Bcl-2 mRNA、 BAX mRNA in order to find a new
[Background]Myocardial protection is an extremely important subject and has been studied all through in cardiac surgical region. Application of various cardioplegia have significantly improved the myocardial protective effect and surgical results but none of them is perfect.The problem of myocardial ischemia-reperfusion injury(MIRI) is not yet resolved ultimately.With the extensive development of thrombolysis, coronary artery bypass grafting(CABG) and percutaneous transluminal coronary angioplasty(PTCA),more and more clinical and preclinical scholars attach importance to the problem of myocardial ischemia-reperfusion injury. MIRI is relevant to many kinds of factors,in which apoptosis has an extreme affinity with it.Growth hormone is a kind of peptide which includes 191 amino acid,its protection for cultured cardiomyocytes from neonatal rats and for necrotic myocardium has been reported ,However,the effects of rGH on myocardial ischemia/reperfusion and the mechanism are not yet clear, So, we designed this subject in order to seek an effective anti-apoptotic agent to attenuate the myocardial ischemia/reperfusion.
[Objective] Using the wistar rat model of myocardial ischemic-reperfusion to probe into the changes of cardiomyocyte apoptotic index and expression of its relative gene at the different timepoint after ischemic-reperfusion.At the same time ,to observe the effect of recombinant human growth hormone( rGH) on cardiomyocyte apoptosis and Bcl-2 mRNA、 BAX mRNA in order to find a new
引文
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