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前列地爾注射液對大鼠心肌缺血再灌注后無復(fù)流的保護(hù)作用和潛在機制

發(fā)布時間:2018-04-13 20:20

  本文選題:前列地爾注射液 + 缺血再灌注; 參考:《吉林大學(xué)》2014年碩士論文


【摘要】:無復(fù)流(no-reflow, NR)作為急性心肌梗死(acute myocardial infarction, AMI)再灌注治療后重要的死亡原因之一,是“心肌有效再灌注”無法實現(xiàn)的最大障礙,但是目前缺乏對其有效的防治手段[1]。因此尋找防治經(jīng)皮冠狀動脈腔內(nèi)介入術(shù)(percutaneouscoronary interventions, PCI)術(shù)后無復(fù)流現(xiàn)象發(fā)生的藥物具有重大意義。 前列地爾又稱前列腺素E1(Prostaglandin E1, PGE1),是多不飽和脂肪酸二高γ-亞油脂酸的氧化產(chǎn)物,具有廣泛的生物活性和藥理作用,包括抑制血小板聚集、擴張血管、促進(jìn)紅細(xì)胞變形等[2]。前列地爾注射液在心腦血管中的應(yīng)用已得到臨床專家的認(rèn)可,針對心絞痛、心肌梗死、腦梗死等疾病都有廣泛的應(yīng)用,加之PCI手術(shù)在臨床上的崛起和醫(yī)生信賴的加深,前列地爾在PCI中的應(yīng)用也成為新興領(lǐng)域,療效獲得部分專家的認(rèn)可,,但其對無復(fù)流的防治作用尚未見報道[3,4]。因此探究前列地爾注射液對心肌缺血再灌注后無復(fù)流的保護(hù)作用及其機制具有重要的臨床應(yīng)用價值。 本研究通過結(jié)扎大鼠冠狀動脈左前降支120min,再灌注120min建立心肌缺血再灌注后無復(fù)流模型,觀察缺血再灌注后各項指標(biāo)的變化,探討前列地爾注射液對大鼠心肌缺血再灌注無復(fù)流的保護(hù)作用及機制。結(jié)果表明,靜脈注射前列地爾注射液4、8μg/kg均能明顯縮小心肌缺血、梗死及無復(fù)流范圍,減輕心肌損傷程度,并能明顯降低血清CK-MB及LDH活性,證實其對大鼠實驗性心肌缺血再灌注無復(fù)流具有治療作用;前列地爾注射液4、8μg/kg均能顯著降低大鼠全血及血漿黏度,降低血漿TXA2含量,升高PGI2及NO含量,提示其可抑制血小板黏附、聚集,增加再灌注時冠狀動脈的開放程度及抑制血液高黏滯狀態(tài),防止血栓形成,增加心肌梗死區(qū)的冠脈動脈血流;前列地爾注射液4、8μg/kg亦能明顯降低血清MDA含量及MPO活性,升高SOD活性,提示其可減弱心肌氧化損傷程度,增加機體的抗氧化能力。 綜上所述,前列地爾注射液對大鼠實驗性心肌缺血再灌注無復(fù)流具有保護(hù)作用,其機制可能與抑制血小板黏附、聚集,增加再灌注時冠狀動脈的開放程度及抑制血液高黏滯狀態(tài),防止血栓形成,減弱心肌氧化損傷程度,增加機體的抗氧化能力有關(guān)。
[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 緯 -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.
【學(xué)位授予單位】:吉林大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2014
【分類號】:R965

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