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右旋2-丙氨酸,5-亮氨酸脑腓肽诱导的心肌冬眠对离体兔心缺血-再灌注损伤的保护作用

The Protective Effect of Myocardial Hibernation Induced by D-Ala(2),D-Leu(5) Enkephalin on Myocardial Ischemia-Reperfusion Injury of Rabbits in Vitro
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摘要 目的观察δ阿片受体激动剂——右旋2-丙氨酸,5-亮氨酸脑腓肽(DADLE)是否具有保护成年兔离体心肌少受或免受缺血-再灌注损伤的作用,以探讨新的心肌保护方法和机制。方法30只兔制作Langendorff离体灌注模型,随机分成3组,每组10只,对照组:采用标准心脏停搏液灌注;组1:标准心脏停搏液+DADLE(1mg/kg)灌注;组2:标准心脏停搏液+纳洛酮(3mg/kg)灌注。3组心脏停搏后分别进行再灌注。检测3组缺血前、后左心室发展压(LVDP)、乳酸脱氢酶(LDH)的变化,在电子显微镜下观察心肌细胞超微结构,应用流式细胞仪检测心肌细胞的凋亡情况。结果缺血后3组间LVDP和LDH比较差异有统计学意义(P<0.05);组1 LVDP高于组2和对照组(69.8±5.8 mmHg vs.23.4±3.9 mmHg;69.8±5.8 mmHg vs.37.9±4.7 mmHg;P<0.05),而LDH低于组2和对照组(1 272.6±59.1 U/L vs.2 764.4±27.7 U/L,1 272.6±59.1 U/L vs.1 884.4±37.5 U/L;P<0.05)。组1心肌细胞凋亡率低于组2和对照组。心肌超微结构显示:组1线粒体结构基本正常;组2线粒体结构损伤严重;对照组线粒体轻度损伤。结论应用DADLE灌注心肌可诱导心肌细胞冬眠,对缺血-再灌注损伤的心肌具有保护作用。 Objective To investigate whether the agonist of delta opoid receptor D-Ala(2) ,D-Leu(5) enkephalin (DADLE) has the effect of decreasing myocardial injury during ischemia-reperfusion of adult rabbits' myocardium,so that a new mechanism and way to myocardial protection could be found. Methods Langendorff model was used during the experiment. Thirty rabbits were divided into three groups randomly (each group 10 rabbits). Control group: St. Thomas Ⅱ cardioplegic solution was used; group 1: St. Thomas Ⅱ cardioplegic solution and DADLE (1mg/ kg) were used; group 2: St. Thomas Ⅱ cardioplegic solution and naloxone(3mg/kg) were used to induce the hearts to arrest respectively. After arrest the hearts were reperfused respectively. Data of left ventricle development pressure (LVDP) was recorded before and after ischemia. Biochemical indicators of myocardium, lactate dehydrogenase(LDH) were detected before and after ischemia. Some myocardial tissues were used to explore the changes of the tissue of uhrastructure with electron microscope, when the experiment was over. Still some myocardial tissues were to be detected by flow cytometer to evaluate the apoptosis of the myocardium. Results The LDH and LVDP showed significant difference among three groups after ischemia(P〈0.05) ; LVDP in group 1 was higher than those in group 2 and control group(69.8±5.8 mmHg vs. 23.4±3.9 mmHg; 69.8±5.8 mmHg vs. 37.9±4. 7 mmHg; P〈0.05), the LDH in group 1 was lower than those in group 2 and control group(1 272.6±59.1 U/L vs. 2 764.4±27.7 U/L, 1 272.6±59.1 U/Lvs. 1 884.4±37.5 U/L; P〈0.05). The apoptosis rate in group 1 was lower than those in group 2 and control group. As could be shown from the uhrastructure: mitochondria structure was nearly normal in group 1 ; mitochondria structure was injuried severely in group 2; there was a minor injury in control group. Conclusion Agonist of 3 opoid receptor DADLE in cardioplegic solution could induce hibernation, which has myocardial protection effect during ischemia-reperfusion injury.
出处 《中国胸心血管外科临床杂志》 CAS 2009年第1期48-51,共4页 Chinese Journal of Clinical Thoracic and Cardiovascular Surgery
关键词 右旋2-丙氨酸 5-亮氨酸脑腓肽 心肌顿抑 凋亡 超微结构 D-Ala(2) ,D-Leu(5) enkephalin Myocardial stunning Apoptosis Uhrastructure
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