胺碘酮、厄贝沙坦及其合用对大鼠心肌缺血再灌注损伤保护的对比研究
摘要
目的观察胺碘酮、厄贝沙坦及其合用对大鼠心肌缺血再灌注损伤的保护作用。
方法50只健康雄性Sprague-Dawley大鼠随机分为5组:假手术组、缺血再灌注组、胺碘酮组、厄贝沙坦组、胺碘酮与厄贝沙坦联合用药组。按照实验设计要求,大鼠经过1周预处理后,在心电监护下,冠状动脉左前降支结扎30min,再通冠状动脉120min。记录自心肌缺血至再灌注120min心电图变化,测量并记录再灌注120min时左室舒张末压、收缩压及心率等血流动力学参数。按照LamBeth规则、Stear SE评分系统给予大鼠心肌缺血再灌注时心律失常(室早、室速、室颤)评分。取梗死区心肌组织测量丙二醛含量、超氧化物歧化酶活性。分离出心室并测量心室湿重,用氯化硝基四氮唑蓝染色,称取梗死区心肌重量,以梗死心肌重量占心室湿重百分比计算心肌梗死面积。
结果与假手术组相比,缺血再灌注组及药物干预组缺血再灌注损伤性心律失常(室早、室速、室颤)明显增多,左室舒张末压明显升高,心肌耗氧量明显降低,丙二醛含量明显升高,超氧化物歧化酶活性明显降低,心肌梗死面积明显增大,有明显差异(P<0.05);与缺血再灌注组相比,药物干预组缺血再灌注损伤性心律失常(室早、室速、室颤)明显改善,左室舒张末压明显降低,心肌耗氧量明显降低,丙二醛含量明显降低,超氧化物歧化酶活性明显增高,心肌梗死面积明显减小,有明显差异(P<0.05);与单独用药组相比,联合用药组缺血再灌注损伤性心律失常(室早、室速、室颤)明显改善,左室舒张末压明显降低,心肌耗氧量明显降低,丙二醛含量明显降低,超氧化物歧化酶活性明显增高,心肌梗死面积明显减小,有明显差异(P<0.05);单独用药组间,缺血再灌注损伤性心律失常(室早、室速、室颤)、左室舒张末压、心肌耗氧量、丙二醛含量、超氧化物歧化酶活性、心肌梗死面积无明显差异(P﹥0.05)。
结论胺碘酮、厄贝沙坦及其联合用药可减少再灌注心律失常,降低左室舒张末压,降低心肌耗氧量,降低心肌组织丙二醛含量,增强心肌组织超氧化物歧化酶活性和减少心肌梗死面积,对在体大鼠心肌缺血再灌注损伤有保护作用,联合用药有叠加效应。
Objective In this study we used amiodarone and irbesartan before reperfusion to interfere in myocardial ischemia-reperfusion injury in rat heart and investigated the preventive and therapeutic effect of amiodarone , irbesartan and both combination on myocardial ischemia-reperfusion injury in rat hearts .
Methods 50 Sprague-Dawley male rats are divided into five groups randomly,sham group,ischemia-reperfusion group,amiodarone group (2.5mg/kg.d) ,irbesartan group (30mg/kg.d) , combination of Amiodarone and Irbesartan group. After 1 week of pretreatment, the left anterior coronary descending artery was ligated in 30min,then the ligateing was relieved 120min with hemodynamic and electrocardiographic monitoring.The ECG changes were recorded incessantly from myocardial ischemia to reperfusion and the left ventricle hemodynamic parameters were recorded in the end. The ECG was analysed and given score in LamBeth regulation. Myocardial tissue of infarcted zone was scissored to measure MDA content and SOD activity. The tissue sections were stained by N-BT and weighed.
Results The scores of ischemia reperfusion arrhythemias(VP,VT or VF) , hemodynamic variables ,myocardiol relative infarct weight, the levels of tissue SOD activity and MDA content,myocardial infarction size were significant different among sham group, ischemia reperfusion group and drug intervention group (P<0.05),and were different between groups Amiodarone,Irbesartan and combination of Amiodarone and Irbesartan(P<0.05) too,but were no significant different between Amiodarone group and Irbesartan group(P﹥0.05).
Conclusion Amiodarone and Irbesartan have significant prevention effects on rat model of myocardium ischemia-reperfusion injury.There is additive effect when the two drugs were used in combination.
方法50只健康雄性Sprague-Dawley大鼠随机分为5组:假手术组、缺血再灌注组、胺碘酮组、厄贝沙坦组、胺碘酮与厄贝沙坦联合用药组。按照实验设计要求,大鼠经过1周预处理后,在心电监护下,冠状动脉左前降支结扎30min,再通冠状动脉120min。记录自心肌缺血至再灌注120min心电图变化,测量并记录再灌注120min时左室舒张末压、收缩压及心率等血流动力学参数。按照LamBeth规则、Stear SE评分系统给予大鼠心肌缺血再灌注时心律失常(室早、室速、室颤)评分。取梗死区心肌组织测量丙二醛含量、超氧化物歧化酶活性。分离出心室并测量心室湿重,用氯化硝基四氮唑蓝染色,称取梗死区心肌重量,以梗死心肌重量占心室湿重百分比计算心肌梗死面积。
结果与假手术组相比,缺血再灌注组及药物干预组缺血再灌注损伤性心律失常(室早、室速、室颤)明显增多,左室舒张末压明显升高,心肌耗氧量明显降低,丙二醛含量明显升高,超氧化物歧化酶活性明显降低,心肌梗死面积明显增大,有明显差异(P<0.05);与缺血再灌注组相比,药物干预组缺血再灌注损伤性心律失常(室早、室速、室颤)明显改善,左室舒张末压明显降低,心肌耗氧量明显降低,丙二醛含量明显降低,超氧化物歧化酶活性明显增高,心肌梗死面积明显减小,有明显差异(P<0.05);与单独用药组相比,联合用药组缺血再灌注损伤性心律失常(室早、室速、室颤)明显改善,左室舒张末压明显降低,心肌耗氧量明显降低,丙二醛含量明显降低,超氧化物歧化酶活性明显增高,心肌梗死面积明显减小,有明显差异(P<0.05);单独用药组间,缺血再灌注损伤性心律失常(室早、室速、室颤)、左室舒张末压、心肌耗氧量、丙二醛含量、超氧化物歧化酶活性、心肌梗死面积无明显差异(P﹥0.05)。
结论胺碘酮、厄贝沙坦及其联合用药可减少再灌注心律失常,降低左室舒张末压,降低心肌耗氧量,降低心肌组织丙二醛含量,增强心肌组织超氧化物歧化酶活性和减少心肌梗死面积,对在体大鼠心肌缺血再灌注损伤有保护作用,联合用药有叠加效应。
Objective In this study we used amiodarone and irbesartan before reperfusion to interfere in myocardial ischemia-reperfusion injury in rat heart and investigated the preventive and therapeutic effect of amiodarone , irbesartan and both combination on myocardial ischemia-reperfusion injury in rat hearts .
Methods 50 Sprague-Dawley male rats are divided into five groups randomly,sham group,ischemia-reperfusion group,amiodarone group (2.5mg/kg.d) ,irbesartan group (30mg/kg.d) , combination of Amiodarone and Irbesartan group. After 1 week of pretreatment, the left anterior coronary descending artery was ligated in 30min,then the ligateing was relieved 120min with hemodynamic and electrocardiographic monitoring.The ECG changes were recorded incessantly from myocardial ischemia to reperfusion and the left ventricle hemodynamic parameters were recorded in the end. The ECG was analysed and given score in LamBeth regulation. Myocardial tissue of infarcted zone was scissored to measure MDA content and SOD activity. The tissue sections were stained by N-BT and weighed.
Results The scores of ischemia reperfusion arrhythemias(VP,VT or VF) , hemodynamic variables ,myocardiol relative infarct weight, the levels of tissue SOD activity and MDA content,myocardial infarction size were significant different among sham group, ischemia reperfusion group and drug intervention group (P<0.05),and were different between groups Amiodarone,Irbesartan and combination of Amiodarone and Irbesartan(P<0.05) too,but were no significant different between Amiodarone group and Irbesartan group(P﹥0.05).
Conclusion Amiodarone and Irbesartan have significant prevention effects on rat model of myocardium ischemia-reperfusion injury.There is additive effect when the two drugs were used in combination.
引文
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