银杏内酯A对缺血/再灌注损伤的大鼠心功能的影响

Effects of ginkgolide A on the function of heart from ischemia-reperfuion rats

目的探讨银杏内酯A(Ginkgolide A,GA)对离体大鼠心肌缺血/再灌注(ischemia/reperfusion,I/R)损伤的心功能的影响。方法 Langendorff灌注离体大鼠心脏,用停灌复灌的方式制备心肌缺血/再灌注损伤模型,记录左心室收缩峰压(LVSP)、左心室舒张末压(LVEDP)、收缩压和舒张压最大变化速率(±LVdp/dtmax)和心率(HR)的变化,并测定复灌后冠状动脉流出液中LDH和SOD的含量及心肌梗死面积。分离单个细胞进行GA预处理,模拟缺血/再灌注培养后检测心肌细胞存活率和单个心肌细胞的收缩幅度。结果 GA预处理以后,LVSP、-dp/dtmax和HR在复灌10 min时较缺血/再灌注组具有明显的改善(P<0.05),并增加心率,减少LDH的生成,增加SOD的活性,降低心肌梗死面积。经GA预处理的心肌细胞存活率明显提高,10μmol.L-1GA能够明显提高缺血后单个心肌细胞的收缩幅度。结论 GA对缺血/再灌注损伤的心肌具有一定的改善作用。

Aim To investigate the effects of ginkgolide A（GA）,ginkgo biloba extract,on the cardiac systolic function of isolated heart subjected to ischemia/reperfusion（I/R） in Sprague-Dawley male rats.Methods Sprague-Dawley rat hearts were quickly removed,mounted on Langendorff apparatus,and perfused with Krebs-Henseleit（KH） solution.After the initial 30 min stabilization period,the rats were randomly divided into 3 groups including control group,ischemia/reperfusion group,ginkgolide A group.Powerlab biological signal system was used to measure the changes of the left ventricular systolic pressure（LVSP）,left ventricular end diastolic pressure（LVEDP）,the maximal rate of pressure increase in systole phase（＋dp/dtmax）,maximal rate of pressure decrease in diastole phase（-dp/dtmax）,and heart rate（HR） continuously.Then the release of lactate dehydrogenase（LDH） and superoxide dismutase（SOD） in the coronary effluent was determined with LDH and SOD kit.After reperfusion,the change of myocardial infarct size was tested.Cardiomyocytes from normal rat hearts were isolated by 5 min of Ca2＋-free buffer perfusion and 25 min of collagenase perfusion.Some myocytes were cultured with ginkgolide A at different concentrations 1.0,5.0,10.0 μmol·L-1,respectively.After simulated IR protocol,the viability and the contraction of cardiomyocytes were measured.Results 10 minutes after the hearts were reperfused,ginkgolide A administration with 10 μmol·L-1 before ischemia led to partial prevention of reperfusion injury by increasing LVSP,decreasing-dp/dtmax,and improving HR compared with IR group（P＆lt;0.05）.To some extent,ginkgolide A perfusion for 10 minutes before ischemia elevated the pulse pressure,heart rate and the activity of superoxide dismutase,meanwhile,decreased the release of lactate dehydrogenase.And ginkgolide A could diminish the myocardial infarct size of hearts compared with IR group.The viability and the contraction of cardiomyocytes were significantly improved by ginkgolide A pretreatment at 10 μmol·L-1.Conclusions Ginkgolide A can partly prevent I/R injury in rat hearts,and improve the cardiac systolic function.