前列地尔注射液对大鼠心肌缺血再灌注后无复流的保护作用和潜在机制

发布时间：2018-04-13 20:20

本文选题：前列地尔注射液 + 缺血再灌注　；参考：《吉林大学》2014年硕士论文

【摘要】：无复流（no-reflow, NR）作为急性心肌梗死（acute myocardial infarction, AMI）再灌注治疗后重要的死亡原因之一，是“心肌有效再灌注”无法实现的最大障碍，但是目前缺乏对其有效的防治手段[1]。因此寻找防治经皮冠状动脉腔内介入术（percutaneouscoronary interventions, PCI）术后无复流现象发生的药物具有重大意义。前列地尔又称前列腺素E1（Prostaglandin E1, PGE1），是多不饱和脂肪酸二高γ-亚油脂酸的氧化产物，具有广泛的生物活性和药理作用，包括抑制血小板聚集、扩张血管、促进红细胞变形等[2]。前列地尔注射液在心脑血管中的应用已得到临床专家的认可，针对心绞痛、心肌梗死、脑梗死等疾病都有广泛的应用，加之PCI手术在临床上的崛起和医生信赖的加深，前列地尔在PCI中的应用也成为新兴领域，疗效获得部分专家的认可，，但其对无复流的防治作用尚未见报道[3,4]。因此探究前列地尔注射液对心肌缺血再灌注后无复流的保护作用及其机制具有重要的临床应用价值。本研究通过结扎大鼠冠状动脉左前降支120min，再灌注120min建立心肌缺血再灌注后无复流模型，观察缺血再灌注后各项指标的变化，探讨前列地尔注射液对大鼠心肌缺血再灌注无复流的保护作用及机制。结果表明，静脉注射前列地尔注射液4、8μg/kg均能明显缩小心肌缺血、梗死及无复流范围，减轻心肌损伤程度，并能明显降低血清CK-MB及LDH活性，证实其对大鼠实验性心肌缺血再灌注无复流具有治疗作用；前列地尔注射液4、8μg/kg均能显著降低大鼠全血及血浆黏度，降低血浆TXA2含量，升高PGI2及NO含量，提示其可抑制血小板黏附、聚集，增加再灌注时冠状动脉的开放程度及抑制血液高黏滞状态，防止血栓形成，增加心肌梗死区的冠脉动脉血流；前列地尔注射液4、8μg/kg亦能明显降低血清MDA含量及MPO活性，升高SOD活性，提示其可减弱心肌氧化损伤程度，增加机体的抗氧化能力。综上所述，前列地尔注射液对大鼠实验性心肌缺血再灌注无复流具有保护作用，其机制可能与抑制血小板黏附、聚集，增加再灌注时冠状动脉的开放程度及抑制血液高黏滞状态，防止血栓形成，减弱心肌氧化损伤程度，增加机体的抗氧化能力有关。
[Abstract]:Non-reflow no-reflow (NRR) is one of the most important causes of death after acute myocardial reperfusion in acute myocardial infarction (AMI). It is the biggest obstacle that can not be achieved by effective myocardial reperfusion. However, there is a lack of effective prevention and treatment for it at present [1].Therefore, it is of great significance to search for drugs to prevent and treat percutanous coronary interventionsafter percutaneous coronary intervention (PCI) without reflow.Prostaglandin E1(Prostaglandin E1 (PGE1) is the oxidation product of polyunsaturated fatty acid dihigh 纬 -lipids. It has a wide range of biological activities and pharmacological effects, including inhibition of platelet aggregation, vasodilation and erythrocyte deformability [2].The application of alprostadil injection in cardiovascular and cerebrovascular diseases has been recognized by clinical experts. It has been widely used for angina pectoris, myocardial infarction, cerebral infarction and other diseases, in addition to the rise of PCI surgery in clinic and the deepening of doctors' trust.The application of alprostadil in PCI has also become a new field, the curative effect has been recognized by some experts, but its preventive and therapeutic effect on no reflux has not been reported [3 / 4].Therefore, to explore the protective effect of alprostadil injection on myocardial ischemia reperfusion without reflow and its mechanism has important clinical application value.In this study, the left anterior descending coronary artery was ligated for 120 minutes and reperfusion 120min was used to establish the model of no reflow after myocardial ischemia and reperfusion, and to observe the changes of indexes after ischemia reperfusion.To investigate the protective effect and mechanism of alprostadil injection on myocardial ischemia reperfusion in rats.The results showed that intravenous injection of 4 渭 g/kg alprostadil could significantly reduce myocardial ischemia, infarct and no reflow, reduce the degree of myocardial injury, and decrease the activities of serum CK-MB and LDH.It is proved that it has therapeutic effect on experimental myocardial ischemia-reperfusion in rats, and alprostadil injection of 48 渭 g/kg can significantly reduce the viscosity of whole blood and plasma, decrease the content of plasma TXA2, and increase the contents of PGI2 and no.The results suggest that it can inhibit platelet adhesion and aggregation, increase the open degree of coronary artery during reperfusion, inhibit blood hyperviscosity, prevent thrombosis and increase coronary artery flow in myocardial infarction area.Alprostadil injection 48 渭 g/kg also significantly decreased serum MDA content and MPO activity, and increased SOD activity, suggesting that it could weaken the degree of myocardial oxidative damage and increase the antioxidant capacity of the body.In conclusion, alprostadil injection has no protective effect on experimental myocardial ischemia-reperfusion injury in rats, and its mechanism may be associated with inhibition of platelet adhesion and aggregation.It is related to increasing the opening degree of coronary artery during reperfusion, inhibiting the hyperviscosity of blood, preventing thrombosis, weakening the degree of myocardial oxidative injury and increasing the antioxidant ability of body.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965

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