粒细胞集落刺激因子治疗急性心肌梗死的实验研究

The experimental study of repairing acute infarcted myocardium by injection of granulocyte colony-stimulating factor in swine

目的探讨注射人重组粒细胞集落刺激因子(granulocytecolony-stimulatingfactorG-CSF)动员自体骨髓干细胞对实验急性心肌梗死作用。方法健康杂种猪6头,结扎左冠状动脉前降支距终末端1/3稍高处制成心肌梗死模型,随机分为治疗组及对照组。治疗组注射G-CSF,对照组注射等容积的生理氯化钠溶液。于术前、术后1日、2日、术后1周及术后4周分别测肌酸激酶及其同工酶。术前、术后1周及术后4周分别测左心室射血分数及心肌梗死面积。4周后取出心脏,作病理检查,测定心肌毛细血管密度及对心肌增殖细胞计数。结果治疗组心肌梗死面积缩小,左心室射血分数提高,和对照组比较有统计学意义(P<0.05);治疗组每视野梗死区血管数为(6.2±2.2)根,而对照组为(2.7±1.8)根,差异有统计学意义(P<0.01);治疗组梗死区每视野增殖细胞(Ki-67阳性)数为(5.1±1.4)个,而对照组为(2.4±1.3)个,差异有统计学意义(P<0.01);术后第1天猪心肌肌酸激酶及其同工酶达到高峰,以后逐渐下降,在术后4周基本下降到正常水平。治疗组和对照组差异无统计学意义(P>0.05)。结论注射G-CSF可缩小心肌梗死面积,改善心射血功能,促进心肌梗死处血管再生及细胞增殖,对心肌酶学无明显影响。

Objectives To evaluate the effects by injection of granulocyte colony-stimulating factor （G-CSF） into a swine model with acute myocardial infarction. Methods Six pigs weighing 18 to 22.5 kg were ligated the distal 1/3 of the left anterior descending （LAD）, the survival of animals were randomly divided into 2 groups： 3 pigs received G-CSF, another 3 pigs received saline instead of G-CSF. Blood was obtained from the femoral vein. Plasma levels of cardiac creatine kinase （CK） and creatine kinase （CK-MB）were detected at before operation, immediately after operation and one day, two days, one week, and four weeks later respectively. The infarcted area and global left ventricular function （LVEF） were measured before operation and one week, four weeks later. Four weeks later, the hearts of swine were taken out to make slides for pathological examination. Blood vessel density and the number of proliferating cells were calculated. Results The cardiac function improved and the infarcted area reduced after AMI evidently by injecting G-CSF. Blood vessel density and the number of Ki-67 positive cells in G-CSF group were higher than that of control group. Time-dependent changes in plasma levels for cardiac enzymes （creatine kinase and creatine kinase-MB）did not differ between the G-CSF group and control group. Conclusions The current study shows that injection of G-CSF into a swine model with acute myocardial infarction can mobilize bone marrow stem cells to reduce infarction size, improve cardiac function, promote blood vessel regeneration and cell proliferation, but it can not affect myocardium enzyme in evidence.