银杏内酯B对心肌缺血再灌注心律失常大鼠的作用及机制研究

摘要

目的 观察银杏内酯B对心肌缺血再灌注所致心律失常大鼠的保护作用并探讨其机制.方法 取120只SD大鼠随机分为假手术组、模型组、维拉帕米组2.5 mg/(kg·d)(阳性药物)及银杏内酯B低、中、高剂量组[15、30、60 mg/(kg·d)]组,每组各20只.术前7d连续腹腔注射给药,每日1次,最后1次给药2h后,采用结扎冠状动脉前降支的方法建立心肌缺血再灌注性心律失常大鼠模型,行Ⅱ导联心电图监测并记录,计算心律失常发生率、行心律失常评分;测定心肌组织Na+-K+-ATPase、Ca2+-Mg2+-ATPase活性,测定心肌组织Ca2+浓度;测定心肌组织抗氧化酶活性和MDA含量.结果 与模型组比较,银杏内酯B 30、60 mg/(kg·d)组和维拉帕米2.5 mg/(kg·d)组心电图PR间期、QRS间期显著延长且ST段抬高程度显著降低(P＜ 0.05或P＜0.01);室性心动过速(VT)、室颤(VF)发生率显著降低(P＜ 0.05或P＜0.01),心律失常评分显著降低(P＜ 0.05或P＜0.01),心肌组织Na+-K+-ATPase、Ca2+-Mg2+-ATPase活性显著升高(P＜ 0.05或P＜0.01),Ca2+浓度显著降低;抗氧化酶[超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)]活性显著升高且MDA含量显著降低(P＜ 0.05或P＜0.01).结论 银杏内酯B对心肌缺血再灌注性心律失常大鼠具有一定的保护作用,机制可能与银杏内酯B提高ATPase活性、降低心肌组织Ca2+浓度、降低氧化应激损伤有关.%Objective:To study the protective effects and its mechnism of Ginkgolide B (GB) on myocardial arrhythmia induced by myocardial ischemia-reperfusion.Methods:120 SD rats were randomly divided into sham operation group,the model group and GB [15,30,60 mg/(kg·d)] groups and Verapamil 2.5 mg/kg group(positive control group),n =20.The drugs were given by intragastric administration for 7 d,2 h after the last time,and the rat model of myocardial ischemia-reperfusion arrhythmia was established by ligation of anterior descending coronary artery,line Ⅱ lead electrocardiogram monitoring and recording,the incidence of arrhythmia was calculated and scored;the activity of Na+-K+-ATPase and Ca2+-Mg2+-ATPase and the content of Ca2+ in myocardium were measured;the activities of antioxidant enzymes and the content of MDA in myocardium were measured.Results:Compared with the model group,the PR interval,QRS interval of GB [30,60 mg/(kg·d)] groups and and Verapamil 2.5 mg/kg group were significantly longer and the ST segment elevation was significantly decreased(P＜ 0.05 or P＜ 0.01);the incidence rate of VT,VF and the arrhythmia score was significantly decreased (P＜ 0.05 or P＜0.01);the activity of of Na+-K+-ATPase and Ca2+-Mg2+-ATPase were significantly increased (P＜0.05 or P＜0.01);the content of Ca2+ was significantly decreased (P＜ 0.05 or P＜ 0.01);the activity SOD,GSH-Px in myocardium were significantly increased and the content of MDA were significantly decreased (P＜0.05 or P＜ 0.01).Conclusion:GB has a protective effect on reperfusion arrhythmia induced by myocardial ischemia,which is perhaps related to its effects of improving ATPase activity,reducing Ca2+ concentration and inhibiting oxidative stress injury.