目的 观察银杏内酯B对大鼠离体心脏缺血再灌注损伤的保护作用并探讨其机制.方法 选取120只SD大鼠随机分为正常对照组、模型组、银杏内酯B(15、30、60 mg/kg)组与维拉帕米组(阳性药物对照组)各20只;手术前2h腹腔注射给药,正常对照组和模型组同步给予0.9％氯化钠注射液.采用Langendorff灌流系统建立离体心脏灌注模型,正常对照组持续灌注Krebs-Henseleit液(K-H液),模型组、银杏内酯B各剂量组和维拉帕米组平衡灌注20 min后停灌30 min、再灌注60 min后行各指标检测.测定冠脉流出液心肌酶活性;TTC染色测定心脏组织梗死面积,HE染色观察心脏组织病变;测定血流动力学指标;测定心肌组织中抗氧化酶活性以及丙二醛(MDA)含量;测定心肌组织ATPase活力.结果 与模型组比较,银杏内酯B 30、60 mg/kg组和维拉帕米组大鼠血清谷草转氨酶(AST)、乳酸脱氢酶(LDH)和肌酸激酶同工酶(CK-MB)活性均显著降低(P＜ 0.05或P＜0.01),心脏组织梗死面积显著降低(P＜0.01),心脏组织病变明显改善,心率(HR)、左室收缩压(LVSP)、左室收缩压最大上升速率(+dP/dtmax)、左室舒张压最大下降速率(-dP/dtmin)均显著升高且左室舒张末压(LVEDP)显著降低(P＜ 0.05或P＜0.01),抗氧化酶[超氧化物歧化酶(SOD)、过氧化氢酶(CAT)]活性显著升高且MDA含量显著降低(P＜ 0.05或P＜0.01),Na+-ATPase、Ca2+-ATPase酶活力显著升高(P＜ 0.05或P＜0.01).结论 银杏内酯B可能通过改善血液流变学指标、降低氧化应激损伤、改善ATPase活力而对大鼠离体心脏表现出一定的保护作用.

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.