银杏内酯B对大鼠心肌缺血再灌注损伤的保护作用及机制研究  

Study on Protection of Ginkgolide B Against Myocardial Ischemia Reperfusion Injury and Its Mechanism

作　　者：熊年[1] 韦晟[2] 

机构地区：[1]安吉县人民医院,浙江安吉313300 [2]南京市鼓楼医院,南京210000

出　　处：《中国现代应用药学》2015年第3期289-294,共6页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的探讨银杏内酯B(ginkgolide B,GB)对心肌缺血再灌注损伤大鼠模型的心肌保护作用及其保护机制。方法建立大鼠心肌缺血再灌注模型,100只SD大鼠随机分为5组:假手术组,缺血再灌注模型组,GB高、中、低剂量组(60.0,30.0,15.0mg·kg-1),每组20只,于手术前灌胃给药7d。通过开胸结扎冠状动脉左前降支30min后松开再灌注,形成心脏局灶缺血再灌注模型。造模48h后检测心功能变化,染色计算梗死面积,病理切片染色评价氧化应激的程度,RT-PCR和Western blot分别监测心肌细胞中凋亡相关蛋白Bcl-2、Bax的变化,及p-Erk、p-Jnk、p-p38磷酸化水平变化。结果 GB预处理能显著改善大鼠缺血再灌注损伤后的心功能;GB中、高剂量组可显著降低Erk,Jnk及p38磷酸化;激活抗凋亡和抗氧化通路,发挥对心肌缺血再灌注的保护作用。结论在缺血再灌注前连续给药GB能缩小缺血再灌注损伤造成的梗死面积,改善心功能。这一保护作用可能是通过抗氧化和抗凋亡信号通路综合作用实现的。OBJECTIVE To study the cardioprotective effect of ginkgolide B（GB） against myocardial ischemia-reperfusion injury（MIRI） in rats.METHODS All of 100 rats were randomly allocated into five groups： sham group（n=20）,model group（n=20）,GB low,medium andhigh dosage groups（for each group,n=20）.Previous to the operation,rats were orally administrated with drugs for continuous 7 days.During the operation,the left anterior descending coronary artery was ligated for 30min before reperfusion,except for the rats in sham groups.After 48h,myocardial function was detected,followed with measuring the infracted areas.The degree of oxidative stress around the damaged area was analyzed by immunohistochemical staining.The expression of apoptosis-related proteins Bcl-2 and Bax,combined with the phosphorylation level of pro-inflammation proteins Erk,Jnk and p38 were detected with PCR or Western blot.RESULTS GB preconditioning significantly alleviated MIRI and post-injury myocardial function.Compared with model group,the phosphorylation level of pro-inflammation proteins were significantly decreased,as well as the oxidative stress level around coronary tissue measured with DHE staining.CONCLUSION In MIR model of rats,GB pre-treatment can significantly protect myocardial damage by anti-oxidative and anti-apoptosis comprehensive pathways.

关 键 词：银杏内酯B 心肌缺血再灌注损伤 抗氧化 抗凋亡 

分 类 号：R285.5[医药卫生—中药学]