银杏内酯B对大鼠离体心脏缺血再灌注损伤的保护作用

Protective Effect of Ginkgolide B on Ischemia-reperfusion Injury in Isolated Rat Heart

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2 h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/dt_(max))、左室舒张压最大下降速率(-dP/dt_(min))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、Ca^(2+)-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 effect of Ginkgolide B(GB)on ischemia-reperfusion injury in isolated rat heart and to explore its possible mechanism.Methods:120 SD rats were randomly divided into the normal control group,the model group,GB(15,30,60 mg/kg)groups and Verapamil 2.5 mg/kg group(positive control group)(n=20).2 h before surgery,the drugs were given by intraperitoneal injection;the normal control and the model groups were given saline.The heart perfusion model was established with Langendorff perfusion system,and the normal control group continued to be given infusion of K-H solution,while the model group and salvia miltiorrhiza polyphenolic acid group were perfused for 20 min,and then subjected ischemia for 30 min,followed by a 60 min reperfusion period.The myocardial enzyme activity in coronary effluent were determined;TTC staining was used to measure the myocardial infarct size were measured by TTC staining,and the cardiac tissue lesions were observed by HE staining;the hemodynamic parameters were determined;the activities of antioxidant enzymes and malondialdehyde(MDA)in myocardium were measured;the activity of ATPase in myocardium was measured.Results:Compared with the model group,the activity of AST,LDH and CK-MB of GB 30,60 mg/kg groups and Verapamil 2.5 mg/kg group were significantly increased(P<0.05 or P<0.01);the cardiac tissue infarct size were significantly reduced(P<0.01),cardiac lesions were significantly improved;the hemodynamic parameters were significant improved:the HR,LVSP,+dP/dt_(max),-dP/dt_(min) were significantly increased and LVEDP was significantly decreased(P<0.05 or P<0.01);the activity of SOD,CAT in myocardium were significantly increased and the content of MDA were significantly decreased(P<0.05 or P<0.01);the activity of Na^(+)-ATPase,Ca^(2+)-ATPase were significantly increased(P<0.05 or P<0.01).Conclusion:GB may play a protective role in isolated rat heart by improving hemorheology,reducing oxidative stress injury and improving ATPase activity.