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目的研究硝酸甘油耐受对缺血再灌注动脉损伤的影响及其机制。方法雄性SD大鼠尾静脉给予硝酸甘油(60μg·kg-1·h-1)或生理盐水12 h,测量平均动脉压和离体血管张力以确定硝酸甘油耐受是否产生。耐受大鼠的离体动脉随机接受以下处理:(1)模拟缺血再灌注,(2)模拟缺血再灌注+还原型谷胱甘肽(GSH,终浓度0.1 mmol/L),(3)对照处理(n=16-18)。未产生耐受的大鼠随机接受模拟缺血再灌注或对照处理(n=16-18)。为了确定硝酸甘油耐受对缺血再灌注血管损伤和内皮功能的影响,检测各组再灌注液中一氧化氮含量、肌酸激酶(CK)和乳酸脱氢酶(LDH)活性,并观测血管收缩功能和对乙酰胆碱的反应。免疫组化标记血管中的硝基化酪氨酸(过氧亚硝基阴离子标志物),灰度扫描分析标记强度。结果与其他各组相比,接受模拟缺血再灌注处理的硝酸甘油耐受血管内皮功能(乙酰胆碱舒张反应和合成一氧化氮能力)显著下降,组织损伤明显增加(CK、LDH活性增加,血管收缩功能降低),血管内硝基化酪氨酸含量显著升高。GSH显著抑制了硝酸甘油耐受的血管损伤作用。结论实验结果显示硝酸甘油耐受显著增加了缺血再灌注诱导的血管损伤,这种作用可能是过氧亚硝基阴离子介导的。此外,我们的结果还表明GSH不仅降低了硝酸甘油耐受的血管损伤作用,而且抑制了血管内过氧亚硝基阴离子的形成。
Objective To study the effect of nitroglycerin tolerance on arterial injury induced by ischemia-reperfusion and its mechanism. Methods Male SD rats were given nitroglycerin (60μg · kg-1 · h-1) or saline for 12 hours in the tail vein. Mean arterial pressure and isolated vascular tone were measured to determine if nitroglycerin was produced. Rat-tolerant arteries were randomized to receive either (1) simulated ischemia-reperfusion, (2) simulated ischemia-reperfusion plus reduced glutathione (GSH, final concentration 0.1 mmol / L), ) Control treatment (n = 16-18). Non-tolerant rats were randomized to receive either simulated ischemia reperfusion or control treatment (n = 16-18). In order to determine the effect of nitroglycerin tolerance on vascular injury and endothelial function after ischemia-reperfusion, the levels of nitric oxide, creatine kinase (CK) and lactate dehydrogenase (LDH), and blood vessels Contractile function and response to acetylcholine. The nitrotyrosine (peroxynitrite anion marker) in the blood vessels was immunohistochemically labeled and the intensity of the label was analyzed by grayscale scanning. Results Compared with the other groups, the nitroglycerin treated with simulated ischemia-reperfusion had a significant decrease in vascular endothelial function (acetylcholine relaxation and nitric oxide synthesis), a significant increase in tissue damage (increased activity of CK and LDH, vasoconstriction Function decreased), intravascular nitrotyrosine content increased significantly. GSH significantly inhibited the nitroglycerin-resistant vascular injury. Conclusion The experimental results show that nitroglycerin tolerance significantly increases the vascular injury induced by ischemia-reperfusion, and this effect may be mediated by peroxynitrite anion. In addition, our results also show that GSH not only reduces the nitroglycerin-resistant vascular damage but also inhibits intravascular nitroso anion formation.