粒细胞集落刺激因子对家兔心肌缺血再灌注损伤的急性保护作用研究  

Acute cardioprotective effects of granulocyte colony-stimulating factor on myocardial ischemia reperfusion injury in rabbits heart

作　　者：任淑静[1] 金奇[1] 周建[1] 林长坚[1] 庞旸[1] 张凝[1] 凌天佑[1] 顾刚[1] 沈永初[1] 陈颖[1] 陆林[1] 吴立群[1] 

机构地区：[1]上海交通大学附属瑞金医院心脏科,200025

出　　处：《中华心律失常学杂志》2011年第5期363-368,共6页Chinese Journal of Cardiac Arrhythmias

基　　金：国家自然科学基金（81070266,81000081）;上海市科委课题（10140903100）;上海市教委创新团队二期项目资助

摘　　要：目的 探讨静脉用粒细胞集落刺激因子（granulocyte colony-stimulating factor,G-CSF）对家兔缺血再灌注心肌是否有急性保护作用,既能否增加心肌保护性蛋白磷酸化-丝氨酸/苏氨酸蛋白激酶（ phosphorylation-Akt,p-Akt）的表达及是否具有抑制室性心律失常作用.方法 14只家兔随机平均分为2组（G-CSF组和对照组,n=7）.所有家兔均开胸结扎冠状动脉左前降支30min,再灌注4 h（G-CSF组再灌注同时静脉泵G-CSF 10 μg/kg维持30 min,对照组静脉用生理盐水10 mL/kg维持30 min）.利用60道袜套状电极进行双心室整体心外膜电生理标测.两组分别于基础状态下,缺血时及再灌注4h后通过程序性电刺激诱发心室颤动（VF）,并测定除颤阈值（defibrillation threshold,DFT）.通过快速傅里叶转换技术测定每个标测电极的VF激动频率.应用Curtis-Walker评分系统评价两组再灌注4h内室性心律失常发生情况.ELISA法测定血清肿瘤坏死因子α（TNF-α）和白细胞介素-10（IL-10）的浓度,蛋白质印迹（Western Blot）测定缺血区心肌p-Akt的表达水平.结果 所有家兔均可通过程序性电刺激诱发出稳定VF.与对照组相比,G-CSF显著降低了再灌注室性心律失常分数[（6.3±1.5）对（2.3±2.6）,P=0.038].两组间基础状态下、缺血及再灌注时DFT及VF激动频率差异无统计学意义（P＞0.05）.两组再灌注4h后VF激动频率较基础状态及缺血时降低,差异有统计学意义（P＜0.05）.G-CSF不增加血清TNF-α及IL-10的浓度,但可增加缺血区心肌P-Akt的表达.结论 静脉用G-CSF未改变VF激动频率及缺血再灌注DFT,但是G-CSF通过增加缺血区心肌组织中p-Akt的表达可减少心肌损伤,减少再灌注心律失常.研究结果提示静脉使用G-CSF对缺血再灌注心肌具有一定的急性保护作用.Objective The aim of this study is to determine whether granulocyte colony-stimulating factor （G-CSF） has acute protection on myocardial ischemia reperfusion injury in rabbit heart by increasing the expression of phosphorylation-Akt,and thus,decreases the incidence of ventricular arrhythmias.Methods In the fourteen open-chest rabbits,left anterior descending coronary artery （LAD） was occluded for 30 minutes followed by 4 hours of reperfusion.Rabbits were randomly assigned into the following two groups：（ 1 ） G-CSF group：intravenously administrating G-CSF （ 10 μg/kg） for 30 minutes ; （2） control group：intravenously administrating normal saline from the onset of reperfusion.A sock containing 60 electrodes was placed over the entire ventricular epicardium for electrical mapping.Ventricular fibrillation （VF） was induced and defibrillation threshold （DFT） was determined and compared at baseline,ischemia and reperfusion stage between the two groups.The activation rate was estimated by Fast Fourier Transform analysis of VF at each electrode.Curtis and Walker Arrhythmia Scoring system was used to evaluate the reperfusion ventricular arrhythmia among the 4 hours of reperfusion.The serum concentration of TNF-α and IL-10 were measured by ELISA.The expression of p-Akt was evaluated by western blot analysis in the myocardial ischemic zone.Results VF can be induced by programmed electrical stimulation in each rabbit.Compared to control,G-CSF significantly reduced the arrhythmia score[ （6.3±1.5）vs.（2.3±2.6）,P=0.038].The DFT and VF activation rate were not significantly different at baseline,ischemia and reperfusion stage between the two groups （ P〉0.05）.Compared to the baseline and ischemia stage,the activation rate of VF decreased obviously at the reperfusion stage （ P〈0.05 ）.The blood concentration of TNF-α and IL-10 were not changed,but P-Akt was more strongly activated in the ischemic zone by intravenously administrating G-CSF.Conclusion Intravenous administration of

关 键 词：粒细胞-集落刺激因子 缺血再灌注 再灌注心律失常 心室颤动 除颤阈值 

分 类 号：R541.7[医药卫生—心血管疾病]