粒细胞集落刺激因子联合缺血后适应治疗急性心肌梗死的实验研究

Cardiac protective effect of granulocyte colony-stimulating factor combined with ischemic postconditioning on acute myocardial infarction in rabbits

目的:探讨粒细胞集落刺激因子(G-CSF)联合缺血后适应(IP)对实验兔急性心肌梗死的心脏保护作用。方法:将兔结扎左室支(LVA)后分为4组:缺血再灌注模型组(IR组,松结后直接再灌注)、G-CSF组(松结并于术后12 h开始使用G-CSF皮下注射)、IP组(予以IP行改良再灌注)和G-CSF+IP组(联合应用IP及G-CSF干预)。观察各组术中心电图ST段变化,检测手术前后血常规和心肌钙蛋白I(cTnI),术后4周行超声心动图检查,测定各组梗死心肌的面积、组织病理结构和细胞凋亡。结果:IP组术中ST段回落快于模型组;G-CSF处理后,实验动物血常规中白细胞明显增高;IP组、G-CSF组及联合治疗组术后7 d的cTnI明显低于模型组;术后4周超声心动图结果显示,IP组、G-CSF组及联合治疗组指标好于模型组,联合治疗组最佳;IP组、G-CSF组及联合治疗组梗死心肌面积均明显低于模型组,梗死周边细胞凋亡程度低、血管密度高,联合治疗组最好。结论:G-CSF联合IP可有效减轻心肌梗死后急性期的再灌注损伤,有利于恢复期的心脏修复。

AIM： To investigate the protective effect of granulocyte colony-stimulating factor（G-CSF） combined with ischemic postconditioning（IP） on acute myocardial infarction（AMI）.METHODS： Male New Zealand rabbits were randomly divided into 4 groups（n=15） after 30 min of left ventricular artery（LVA） occlusion： the rabbits in ischemia-reperfusion（IR） group were directly given reperfusion;the rabbits in G-CSF group were subsequently treated with G-CSF（10 μg·kg-1·d-1） by subcutaneous injection after direct reperfusion;the rabbits in IP group received 4 episodes of 30 s reperfusion and 30 s occlusion before total reperfusion;the rabbits in IP combined with G-CSF（IP＋G-CSF） group were treated with both IP and G-CSF.Electrocardiogram（ECG） monitoring was performed during the operation.Blood was drawn to evaluate white blood cell count（WBC） and cardiac troponin I（cTnI） before operation and 7 d later.Ultrasound cardiography was performed to evaluate left ventricular remodeling and functions 4 weeks after operation.The sizes of infarcted myocardium were determined by triphenyltetrazolium chloride（TTC） staining.Apoptosis of cardiomyocytes was measured by terminal deoxynucleotidyl transferase（TdT）-mediated dUTP-biotin nick end labeling（TUNEL） staining.RESULTS： ST-segment resolutions were significantly decreased in IP group and IP＋G-CSF group compared with direct reperfusion groups（P0.05）.WBC significantly increased in the groups treated with G-CSF for 1 week.The values of cTnI after operation were significantly lowered in G-CSF group,IP group and IP＋G-CSF group as compared with IR group（P0.05）.Left ventricular ejection fraction,the size of infarcted myocardium and apoptosis of cardiomyocytes were better in IP group,G-CSF group and IP＋G-CSF group than those in IR group.CONCLUSION： G-CSF combined with IP is a promising strategy against cardiac reperfusion injury and accelerates cardiac repair in AMI.