水飞蓟宾对心肌缺血再灌注性心律失常的影响及机制探索

Protective Effect and Mechanism of Silibinin on Myocardial Arrhythmia Induced by Myocardial Ischemia-reperfusion

目的研究水飞蓟宾(Silibinin,SIL)对大鼠心肌缺血再灌注所致心律失常的保护作用并探索其机制。方法120只实验用SD大鼠随机分为假手术组、模型组、SIL低[100mg/(kg·d)]、中[200mg/(kg·d)]、高[400mg/(kg·d)]剂量组和维拉帕米组[2.5mg/(kg·d)],各20只;术前7天开始灌胃给药(1次/天)。通过结扎冠状动脉前降支复制大鼠心肌缺血再灌注性心律失常模型,监测心电图并观察心律失常情况、进行心律失常评分;测定心肌组织Na^+-K^+ATPase、Ca^2+-Mg^2+ATPase、NOS、抗氧化酶活性和Ca^2+浓度、NO含量、MDA含量。结果较模型组,SIL中、高剂量组和维拉帕米组大鼠心电图PR、QRS间期延长且ST段抬高程度降低;室性心动过速(VT)、心室颤动(VF)发生率降低,心律失常评分降低;Na^+-K^+ATPase、Ca^2+-Mg^2+ATPase活性升高,Ca^2+浓度降低;NOS活性和NO含量均升高;抗氧化酶SOD、GSH-Px活性升高且MDA含量降低;上述差异均有统计学意义(P<0.05)。并且SIL高剂量组部分指标明显优于维拉帕米组。结论SIL对大鼠心肌缺血再灌注所致心律失常具有一定的保护作用,可能与SIL能够改善ATPase活性、降低心肌细胞Ca^2+浓度、提高NO含量、抑制氧化应激等有关。

Objective To study the protective effect of total glucosides of paeony(TGP)on myocardial arrhythmia induced by myocardial ischemia and reperfusion and to explore its mechanism.Methods Totally 120 SD rats were randomly divided into sham operation group,model group and SIL low-,medium-,high-dose[100,200,400mg/(kg·d)]group and Verapamil 2.5 mg/kg group(n=20).The drugs were given by intragastric administration for 7days.2h after the laste time,the rat model of myocardial ischemia-reperfusion arrhythmia was established by ligation of anterior descending coronary artery.LineⅡlead electrocardiogram monitoring and recording,the incidence of arrhythmia was calculated and scored.The activity of Na^+-K^+ATPase and Ca^2+-Mg^2+ATPase and the content of Ca^2+in myocardium were measured.The activities of NOS and the content of NO in myocardium were measured.The activities of antioxidant enzymes and the content of MDA in myocardium were measured.Results Compared with model group,the PR interval,QRS interval of SIL medium-,high-dose and Verapamil groups were significantly longer and the ST segment elevation was significantly decreased.The incidence rate of VT,VF and the arrhythmia score was significantly decreased.The activity of of Na^+-K^+ATPase and Ca^2+-Mg^2+ATPase were significantly increased.The content of Ca^2+and NO were significantly decreased.The activity of NOS and SOD,GSH-Px in myocardium were significantly increased and the content of MDA were significantly decreased.All of the difference above were significant(P<0.05 or P<0.01).And some indicators in the high-dose SIL group were significantly better than those in the verapamil group.Conclusion The SIL has a protective effect on reperfusion arrhythmia induced by myocardial ischemia,which perhaps related to its effects of improving ATPase activity,reducing Ca^2+concentration,increasing NO content and inhibiting oxidative stress injury.