【作者】 张齐好；

【导师】 陆大祥；

【作者基本信息】 暨南大学 ， 病理生理学， 2003， 硕士

【摘要】 目的：甘氨酸(glycine，GLY)是一种最简单的氨基酸。在我们先前的研究中发现，GLY不仅可以直接拮抗内毒素的多种生物学活性，而且还具有保护心脏的作用，能够有效地对抗内毒素所致的心肌损伤及垂体后叶素(pituitrin,Pit)诱导的心肌缺血性损伤。本实验是在上述研究的基础上，进一步探讨GLY对心肌缺血-再灌注损伤(myocardial ischemia-reperfusion,MI/R)的防治作用及机制，为防治缺血性心脏病提供新的思路与方法。 方法：小鼠随机分为5组，以不同药物定时定量灌胃(0.25mL／10g，2次／d)处理。1周后，腹腔注射Pit30U／kg，间隔30min后再腹腔注射硝酸甘油(nitroglycerin,Nit)10mg/kg复制急性MI／R模型。同时记录不同时点的肢体Ⅱ导联心电图，观察小鼠心电图J点及心率的变化。4h后，取出小鼠心脏，分别用比色法和硝酸还原酶法，检测各组小鼠心肌组织中一氧化氮合酶(nitri coxide synthase,NOS)、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)的活性及一氧化氮(nitric oxide,NO)的含量，观察GLY对这些活性物质的影响；用逆转录-多聚酶链式反应(RT-PCR)测定各组小鼠心肌组织Bcl-2 mRNA的表达，观察GLY对其表达量的影响。 结果：心电图结果显示，Pit诱导心肌缺血的动物，心电图J点明显降低，心率明显减慢。MI／R+Gly组在不同时点的J点及心率变化幅度较小，显著小于MI／R组(P＜0.05，P＜0.01)；MI／R+Gly组心肌组织总NOS活性及NO含量升高，而iNOS活性下降，与MI／R组相比，有显著性差异(P＜0.01)；MUR+Gly组Bcl-2扩增产物也较MI／R组明显增多(P＜0.01)。 结论：预防性口服适量GLY有利于保护心脏，减轻MI／R引发的损伤，维持良好的心功能状态。表现在心电图上，GLY降低急性心肌缺血动物心电图J点及心率的变化幅度。GLY的这一作用可能与其增加缺血再灌注心肌组织中NOS的活性及NO的生成，抑制iNOS的活性；促进缺血再灌注心肌Bcl-2 mRNA的表达有关。更多还原

【Abstract】 Objective: Being the simplest amino acid, glycine not only acts as an anti-endotoxin agent, but also has great effects on cytoprotection. It has been demonstrated that glycine protected against myocardial injury induced by endotoxin and acute ischemia in our laboratory works. For contributing to the treatment for ischemic heart disease, the aim of this study was to investigate the protection of glycine against myocardial ischemia-reperfusion and its mechanism.Methods: Mice were randomly divided into five groups and fed with different solution (0.25mL/10g, twice per day). On the 8th day, the mice were injected with pituitrin (30U/kg) and nitroglycerin (10mg/kg, 30 min later) intraperitoneally to remodel acute myocardial ischemia-reperfusion (MI/R). ECG and heart rate were recorded at Omin, 5min, lOmin, 20min, 30min, 40min, 50min. 4h later, the activities of nitric oxide synthase, inducible nitric oxide synthase, and concentrations of nitric oxide in myocardium were examined; The expression of Bcl-2 mRNA in myocardium was also determined by RT-PCR.Results: J point of ECG and heart rate decreased obviously in MI/R-injured mice. Compared to Group MI/R, J point of ECG and heartrate decreased smoothly in Group MI/R+GLY (P<0.05, P<0.01). The activities of NOS and concentrations of NO in Group MI/R+GLY were higher than those in Group MI/R (P<0.01), but the activities of iNOS was lower inversely (P<0.01). In addition, the expression of Bcl-2 mRNA in Group MI/R+GLY was higher than that in Group MI/R (P<0.01).Conclusions: The results suggested that pretreatment of glycine attenuated myocardial ischemia-reperfusion injury induced by pituitrin and nitroglycerin. The mechanism may be related to NOS activation, the increase of NO content, the expression of Bcl-2 mRNA, and the reduction of iNOS in I/R-injured myocardium.更多还原