加速愈合过程和心肌再生可能是心肌梗死后粒细胞集落刺激因子治疗改善心脏功能和重塑的重要机制。
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.
作者信息
Minatoguchi Shinya, Takemura Genzou, Chen Xue-Hai, Wang Ningyuan, Uno Yoshihiro, Koda Masahiko, Arai Masazumi, Misao Yu, Lu Chuanjiang, Suzuki Koji, Goto Kazuko, Komada Ai, Takahashi Tomoyuki, Kosai Kenichiro, Fujiwara Takako, Fujiwara Hisayoshi
机构信息
Second Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa Machi, Gifu, Japan.
出版信息
Circulation. 2004 Jun 1;109(21):2572-80. doi: 10.1161/01.CIR.0000129770.93985.3E. Epub 2004 May 3.
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 microg x kg(-1) x 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 mm2 x slice(-1) x 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 mm2 x slice(-1) x kg(-1), and scar areas 0/0, 0/0, 0/0, and 4.2+/-0.5/7.9+/-0.9* mm2 x slice(-1) x 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.
背景
我们研究了粒细胞集落刺激因子（G-CSF）改善心肌梗死（MI）后心脏功能和重塑的作用，除心肌再生外，是否还与加速愈合过程有关。
方法与结果
在30分钟冠状动脉闭塞和再灌注兔模型中，于MI后1至5天皮下注射生理盐水（S）或10μg·kg⁻¹·d⁻¹的重组人G-CSF（G）。MI后3个月时，G组左心室（LV）尺寸较小、LV射血分数增加且梗死LV壁更厚。在MI后2天、7天、14天和3个月时，G组和S组的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和0/0mm²·切片⁻¹·kg⁻¹，肉芽组织面积分别为0/0、4.0±0.7/8.5±1.0*、3.9±0.8/5.7±0.7和0/0mm²·切片⁻¹·kg⁻¹，瘢痕组织面积分别为0/0、0/0、0/0和4.2±0.5/7.9±0.9mm²·切片⁻¹·kg⁻¹（*P<0.05，G组与S组相比）。MI后7天时，G组巨噬细胞以及基质金属蛋白酶（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吸收，并通过MMP表达减少肉芽组织和瘢痕组织。同时，尽管G组和S组在LV重量、LV壁面积或心肌细胞大小方面无差异，但G组危险区内存活心肌组织面积显著增加。共聚焦显微镜显示G组中3,3,3',3'-四甲基吲哚碳菁高氯酸盐阳性和肌钙蛋白I阳性的心肌细胞明显增加，提示G增强了心肌再生。
结论
愈合过程的加速和心肌再生可能对MI后G-CSF治疗的有益作用起重要作用。
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