银杏叶提取物的心肌延迟保护作用及其机制研究

Delayed cardioprotection of Gingkgo biloba leaf extract and its mechanisms

目的观察银杏叶提取物(EGb761)对大鼠离体心脏心肌的延迟保护作用及其机制。方法离体大鼠心脏全心停灌缺血30min后再灌注30min产生缺血再灌损伤,观测心率(HR)、冠脉流量(CF)、左室内压(LVP)和左室内压变化最大速率(+dp/dtmax),测定心肌组织中肌酸激酶(CK)释放量、心肌组织丙二醛(MDA)和一氧化氮(NO)的量。结果实验前24h单次ig给予EGb761(50或100mg/kg)可显著改善心肌缺血再灌注所致的心功能(LVP和+dp/dtmax)损伤,抑制心肌组织CK释放和MDA水平的增加以及NO水平的降低。预先给予NO合酶抑制剂L-NAME(5mg/kg)或心肌肌细胞膜ATP敏感钾通道(sarcKATP)阻断药HMR1883(3mg/kg),均可明显抑制EGb761对心肌缺血再灌注损伤的延迟保护作用。结论EGb761对缺血再灌注诱导大鼠心肌损伤具有延迟性保护作用,这一保护作用可能与增加NO合成和开放sarcKATP通道有关。

Objective To observe the delayed cardioprotective effect of the extract of Gingkgo biloba leaves （EGb761） and its possible mechanisms in rats. Methods Myocardial ischemia-reperfusion （I/R） injury was induced by 30 min of global ischemia and 30 min of reperfusion in isolated rat hearts. Heart rate （HR）, coronary flow （CF）, left ventricular pressure （LVP）, and its first derivatives （＋dp/dtmax） were recorded, and the releasing content of creatine kinase （CK）, contents of malondialdehyde （MDA） and nitric oxide （NO） in myocardial tissues were measured. Results Single ig EGb761 （50 or 100 mg/kg） at 24 h before I/R were done could significantly attenuate the damage of cardiac function （LVP and -＋dp/ dtmax） and the lowering of NO level in myocardial tissues, and inhibit the increasing in CK release and MDA level induced by I/R in myocardial tissues. The delayed cardioprotective effects of EGb761 were markedly inhibited by pretreatment with L-NAME （5 mg/kg）, an inhibitor of NO synthase, or HMR1883 （3 mg/kg）, an antagonist of sarcolemmal ATP-sensitive potassium channels （sarcKATP）. Conclusion Pretreatment with EGb761 could protect against I/R-induced myocardial injury in rats, and the delayed cardioprotection of EGb761 may be related to increasing in NO production and opening of sarcKATP.