银杏叶提取物EGb761对DPPH自由基所致离体心脏损伤的保护作用研究  

Protective effect of gingkgo biloba leave extract(EGb761) against DPPH free radi cal-induced myocardial damage in isolated rat hearts

作　　者：李年生[1] 何莉梅[1] 于柯南[2] 范若皓[2] 解媛媛[2] 姜德建[1] 

机构地区：[1]中南大学药学院药理学系 [2]中南大学湘雅医学院,长沙410078

出　　处：《中国新药杂志》2009年第17期1677-1681,共5页Chinese Journal of New Drugs

基　　金：国家自然科学基金(30873140);北京市优秀人才培养资助项目(20071D0501600227)

摘　　要：目的:观察银杏叶提取物EGb761对外源性自由基所致离体心脏损伤的保护作用及其机制。方法:离体大鼠心脏采用Langengoff灌流法,记录心率(HR)、冠脉流量(CF)、左室内压(LVP)和左室内压变化最大速率+dp/dtmax,测定肌酸激酶(CK)释放量和心肌组织丙二醛(MDA)和一氧化氮(NO)含量。结果:以含0.25 mol.L-11.1-二苯基-三硝基苯肼(DPPH)的K-H液灌流心脏10 min可显著损伤心功能,表现LVP和+dp/dtmax降低,增加心肌组织CK释放和MDA含量以及NO水平的降低;实验前24 h单次灌胃给予EGb761(100 mg.kg-1)可显著改善DPPH所致的心功能(LVP和+dp/dtmax)损伤,抑制心肌组织CK释放和MDA含量的增加以及NO水平的降低。预先给予NO合酶抑制剂L-NAMA(5 mg.kg-1)、蛋白激酶C(PKC)抑制剂Calphostin C或心肌细胞膜ATP敏感钾通道(sarcKATP)阻断药HMR1883(3 mg.kg-1),均可明显抑制EGb761对DPPH所致心功能损伤的保护作用。结论:EGb761对DPPH所致大鼠心肌损伤具有保护作用,这一保护作用可能与增加NO合成、激活PKC从而引起sarcKATP通道开放有关。Objective： To observe the protective effect of Gingkgo biloba extract（EGb761） on myocardial damage induced by 1,1-diphenyl-2-picrylhygrazyl（DPPH） free radical in isolated rat hearts.Methods： The isolated rat hearts were perfused in a langendirff model.Heart rate（HR）,coronary flow（CF）,left ventricular pressure（LVP） and its first derivatives（dp/dtmax） were recorded,and the activity of creatine kinase（CK） in coronary effluent and contents of malondialdehyde（MDA） and nitric oxide（NO） in myocardial tissues were measured.Results： Perfusion with DPPH（0.25 mol·L^-1） for 10 min caused a significant impairment of cardiac function,as shown by the decreases in LVP,＋dp/dtmax and NO level as well as the increase in CK release.Oral treatment with EGb761（100 mg·kg-1） at 24 h before the experiment was started significantly attenuated the decreases of cardiac function LVP and（dp/dtmax） and NO level in myocardial tissues,and inhibited the increases in CK release and MDA level in DPPH-treated myocardial tissues.The protective effects of EGb761 were markedly inhibited by pretreatment with L-NANE（5 mg·kg^-1）,an inhibitor of NO synthase,Calphostin C（0.1 mg·kg^-1）,an inhibitor of protein kinase（PKC）,or HMR1883（3 mg·kg^-1）,an antagonist of sarcolemmal ATP-sensitive potassium channels（sarcKATP）.Concluslon： EGB761 exerts delayed protection against DPPH-induced myocardial damages in rats,and the protective effect of EGB761 may be related to increasing NO production and activating PKC-sarcKATP pathway.

关 键 词：银杏叶提取物 自由基损伤 心功能实验 ATP敏感钾通道 大鼠 

分 类 号：R972[医药卫生—药品]