Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment
Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment
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DOI：
10.1161/01.cir.0000129770.93985.3e
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发表时间：
2004-06-01
期刊：
影响因子：
37.8
通讯作者：
Fujiwara, H
中科院分区：
文献类型：
--
作者：
Minatoguchi, S;Takemura, G;Fujiwara, H
背景-我们研究了粒细胞集落刺激因子（G-CSF）对心肌梗死（MI）后心功能和重构的改善是否与加速愈合过程以及心肌再生有关。方法与结果：30分钟冠脉闭塞再灌注兔模型，生理盐水(S)或10杯。公斤(1)。心肌梗死后1 ~ 5天皮下注射人重组G- csf (G) d(-1)，心肌梗死后3个月，G组左室（LV）尺寸减小，左室射血分数升高，梗死-左室壁增厚。心肌梗死后2、7、14天和3个月，坏死组织面积分别为14.2 +/- 1.5/13.4 +/- 1.1、0.4 +/- 0.1/1.8 +/- 0.5*、0/0、0/0 mm(2)。片(1)。4.0公斤(1)、造粒地区0/0,+ / - 0.7/8.5 + / - 1.0 * 3.9 + / - 0.8/5.7 + / - 0.7 * 0/0毫米(2)。片(1)。公斤(1),和疤痕区域0/0,0/0,0/0,+ / - 0.5/7.9 + / - 0.9 * 4.2毫米(2)。片(1)。G和S组分别为kg(-1) （* P < 0.05， G对S）。心肌梗死后7天，G中巨噬细胞和基质金属蛋白酶（MMP） 1和9明显增加。这表明G通过增加巨噬细胞加速坏死组织的吸收，并通过MMP的表达减少肉芽组织和疤痕组织。同时，G组在危险区域内存活的心肌组织面积显著增加，尽管G组和s组的左室重量、左室壁面积和心肌细胞大小没有差异。共聚焦显微镜显示，G组中3,3,3',3'-四甲基多碳青高氯酸盐阳性心肌细胞和肌钙蛋白I阳性心肌细胞显著增加。结论-心肌梗死后G-CSF治疗对心肌愈合过程和心肌再生的加速可能起重要作用。
Background - We investigated whether the improvement of cardiac function and remodeling after myocardial infarction (MI) by granulocyte colony - stimulating factor (G-CSF) relates to acceleration of the healing process, in addition to myocardial regeneration.Methods and Results - In a 30-minute coronary occlusion and reperfusion rabbit model, saline (S) or 10 mug . kg(-1) . d(-1) of human recombinant G-CSF ( G) was injected subcutaneously from 1 to 5 days after MI. Smaller left ventricular (LV) dimension, increased LV ejection fraction, and thicker infarct-LV wall were seen in G at 3 months after MI. At 2, 7, and 14 days and 3 months after MI, necrotic tissue areas were 14.2 +/- 1.5/13.4 +/- 1.1, 0.4 +/- 0.1/1.8 +/- 0.5*, 0/0, and 0/0 mm(2) . slice(-1) . kg(-1), granulation areas 0/ 0, 4.0 +/- 0.7/ 8.5 +/- 1.0*, 3.9 +/- 0.8/5.7 +/- 0.7,* and 0/0 mm(2) . slice(-1) . kg(-1), and scar areas 0/ 0, 0/ 0, 0/0, and 4.2 +/- 0.5/ 7.9 +/- 0.9* mm(2) . slice(-1) . kg(-1) in G and S, respectively (* P < 0.05, G versus S). Clear increases of macrophages and of matrix metalloproteinases (MMP) 1 and 9 were seen in G at 7 days after MI. This suggests that G accelerates absorption of necrotic tissues via increase of macrophages and reduces granulation and scar tissues via expression of MMPs. Meanwhile, surviving myocardial tissue areas within the risk areas were significantly increased in G despite there being no difference in LV weight, LV wall area, or cardiomyocyte size between G and S. Confocal microscopy revealed significant increases of cardiomyocytes with positive 3,3,3', 3'-tetramethylindocarbocyanine perchlorate and positive troponin I in G, suggesting enhanced myocardial regeneration by G.Conclusions - The acceleration of the healing process and myocardial regeneration may play an important role for the beneficial effect of post-MI G-CSF treatment.