丙泊酚对罗哌卡因致大鼠心脏毒性及心肌线粒体氧化损伤的保护作用

Protection of Propofol Against Cardiac Toxicity and Oxidative Damage of Myocardial Mitochondria Induced by Ropivacaine in Rats

目的观察丙泊酚对罗哌卡因致大鼠心脏毒性及心肌线粒体氧化损伤的保护作用。方法将36只雄性SD大鼠随机分成3组(n=12),设Ⅰ组(生理盐水组)、Ⅱ组(0.5%丙泊酚)、Ⅲ组(1%丙泊酚)。实验前5 min,Ⅰ组大鼠股静脉注射生理盐水5 m/lkg,Ⅱ组、Ⅲ组大鼠分别股静脉注射0.5%和1%丙泊酚5 m/lkg。以2.5 m/l(kg.min)经大鼠股静脉泵注0.5%罗哌卡因,记录大鼠心律失常和心跳停止时间及罗哌卡因用量;采用差速离心法制备大鼠心肌细胞线粒体,荧光分光光度法测定活性氧(ROS)、硫代巴比妥(TBA)法测定丙二醛(MDA)含量,邻苯三酚自氧化法测定超氧化物酶(SOD)活性、DNTB直接法测定谷胱甘肽过氧化物酶(GSH-Px)活性。结果各组大鼠均有室性心律失常及心跳停止等心脏毒性反应,预注丙泊酚Ⅱ组、Ⅲ组出现心脏毒性的罗哌卡因剂量大于预注生理盐水Ⅰ组的动物(P<0.05),Ⅲ组出现心脏毒性的罗哌卡因剂量大于Ⅱ组(P<0.05)。丙泊酚Ⅱ组、Ⅲ组的ROS、MDA含量低于生理盐水Ⅰ组(P<0.05);Ⅱ组、Ⅲ组心肌线粒体SOD、GSH-Px活性高于Ⅰ组(P<0.05)。结论丙泊酚预处理可减轻罗哌卡因对大鼠的心脏毒性及对大鼠心肌线粒体的氧化损伤作用。

Objective To study the protection of propofol against the cardiac toxicity and the oxidative damage of myocardial mitochondria induced by ropivacaine in rats.Methods Thirty-six male Sprague-Dawley rats were randomly divided into three groups,12 rats for each group.The rats in Group I（control group） received 5mL/kg saline by intravenous injection.The rats in Group Ⅱ and Group Ⅲ were respectively administered with 0.5% and 1.0% propofol at 5ml/kg by intravenous injection.Then all the rats in the three groups were infused with 0.5% ropivacaine at a rate of 2.5ml/kg·min by femoral vein until cardiac arrest occurred.The time points when arrhythmia and cardiac arrest happened were recorded.And the doses of ropivacaine infused by the time points were calculated.The myocardial mitochondria were isolated by differential centrifugation.Thecontents of reactive oxygen species（ROS） and malondialdehyde（MDA） and the activities of mitochondrial superoxide dismutase（SOD） and glutathione peroxidase（GSH-Px） in the mitochondria were detected by fluorescence spectrophotometry,sulfur barbituric acid（TBA）,pyrogallol autoxidation method and DTNB direct method,respectively.Results Infusion of 0.5% ropivacaine induced arrhythmia and cardiac arrest in rats.The doses of ropivacaine that led to arrhythmia and cardiac arrest were remarkably higher in the propofol-pretreated rats than that in the saline-pretreated rats（P0.05）.Moreover,the doses of ropivacaine that resulted in arrhythmia and cardiac arrest were significantly higher in group Ⅲ than those in group Ⅱ（P0.05）.The contents of mitochondrial ROS and MDA in the propofol-pretreated rats were statistically lower than those in the saline-pretreated rats（P0.05）,while the activities of mitochondrial SOD and GSH-Px in the treatment groups were remarkably higher than those in the control group（P0.05）.Conclusions Pre-treatment by propofol can relieve the cardiac toxicity and the oxidative damage of myocardial mitochondria induced by ropivacaine in rats.