粒细胞集落刺激因子对缺血再灌注损伤猪心肌凋亡和心肌纤维化的影响

Effect of hypodermic injection of granulocyte colony-stimulating factor on cardiomyocyte apoptosis and fibrosis after myocardial ischemia-reperfusion in swine

[目的]观察粒细胞集落刺激因子(G-CSF)对缺血再灌注损伤猪心肌细胞凋亡和心肌纤维化的影响。[方法]建立急性缺血再灌注损伤小型猪动物模型,存活12只动物,随机分为对照组和G-CSF治疗组,每组6只。G-CSF治疗组按照5μg/kg.d-1连续7 d皮下注射G-CSF,对照组给予同等量生理盐水。动物模型建成后及治疗后4周分别行冠状动脉造影、左室造影和201TI(铊)核素单光子放射计算机断层显像(SPECT)检查,记录左心室射血分数(LVEF)、左室运动不良节段数目以及心肌灌注损伤指数,并观察心肌凋亡和心肌纤维化情况。[结果]术后4周左室造影显示两组LVEF均改善,分别为(48.9±9.7)%与(52.4±10.1)%,尽管两组间比较差别无显著性意义(P>0.05),但G-CSF治疗可以改善左室局部运动不良节段数(29.4±12.7 vs 20.8±10.3,P<0.05)。SPECT检查结果发现,G-CSF治疗可以减少心肌灌注缺损面积[(26.9±11.8)%vs(13.2±10.1)%,P<0.05]。而且,G-CSF治疗后心脏损伤区域局部心肌凋亡减少的数目比对照组多[(-3.7±1.8)%vs(-1.5±2.0)%],心肌纤维化程度也明显低于对照组,差别有显著性意义(P<0.05)。[结论]G-CSF治疗可以通过降低心肌凋亡和心肌纤维化程度改善缺血再灌注损伤猪心脏功能。

[Objectives] The aim of this study is to investigate the effect of hypodermic injection of granulocyte colony-stimulating factor（G-CSF） on cardiomyocyte apoptosis and fibrosis after myocardial ischemia-reperfusion in swine.[Methods] Twelve swine who were alive underwent myocardial ischemia-reperfusion were randomly assigned into two groups：hypodermic injection of G-CSF（5 μg/kg·d-1） for seven days（G-CSF group,n=6） or administration of saline（control group,n=6）.Measurements were obtained pre-administration and at four weeks post administration,inclu ding coronary angiogram and 201TI-SPECT.Global and regional left ventricular function,myocardial perfusion were evaluated.RT-PCR analysis of Bcl-2 and Bax and collagen staining were used.[Results] No difference was found between the both groups on global left ventricular ejection fraction（LVEF） from angiogram data at four-week follow-up [（48.9±9.7）% vs（52.4±10.1）%,P0.05].However,G-CSF may ameliorate the regional contractility after ischemia-reperfusion（29.4±12.7 vs 20.8±10.3,P0.05）.SPECT also revealed that G-CSF increased myocardial perfusion [（26.9±11.8）% vs（13.2±10.1）%,P0.05].Meanwhile,G-CSF treatment was associated with a significant reduction in myocardial apoptosis [GSF group：（-3.7±1.8）% vs CON group：（-1.5±2.0）%] and an obvious improvement in myocardial fibrosis（P0.05）.[Conclusion] G-CSF could modify the healing process by reduction in apoptosis and fibrosis in a swine ischemia-reperfusion model.