胎儿心肌梗死后的再生性愈合。
Regenerative healing following foetal myocardial infarction.
机构信息
The University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
出版信息
Eur J Cardiothorac Surg. 2010 Dec;38(6):691-8. doi: 10.1016/j.ejcts.2010.03.049. Epub 2010 May 10.
OBJECTIVES
The adult response to myocardial infarction results in inflammation, scar formation, left ventricular dilatation, and loss of regional and global function. Regenerative scarless healing has been demonstrated in foetal dermis and tendon and is associated with diminished inflammation. We hypothesised that following foetal myocardial infarction, there would be minimal inflammation, regenerative healing, and preservation of function.
METHODS
Anteroapical myocardial infarction encompassing 20% of the left ventricle was created in adult or early gestation foetal sheep. Myocardial function was serially assessed using quantitative echocardiography. Infarct architecture was examined histologically for evidence of scar formation. Cellular inflammation, cellular proliferation, and apoptosis were assessed using immunohistochemistry.
RESULTS
In the adult sheep 4 weeks following myocardial infarction, there was a significant decline in ejection fraction (EF) (41±7.4% to 26±7.4%, p<0.05), and the akinetic myocardial segment increased in size (6.9±0.8 cm to 7.9±1.1 cm, p<0.05). By contrast, there was no decline in the foetal EF (53±8.1% to 55±8.8%) and no akinetic foetal myocardial segment 4 weeks post-infarction. The foetal infarcts lacked an inflammatory cell infiltrate and healed with minimal fibrosis, compared with the adults. Foetal infarcts also demonstrated 5-bromo-2'-deoxyuridine (BrdU)+ proliferating cells, including cardiomyocytes, within the infarct.
CONCLUSIONS
These data demonstrate that the foetal response to myocardial infarction is dramatically different from the adult and is characterised by minimal inflammation, lack of fibrosis, myocardial proliferation and restoration of cardiac function. Diminished inflammation is associated with foetal regenerative cardiac healing following injury. Understanding the mechanisms involved in foetal myocardial regeneration may lead to applications to alter the adult response following myocardial infarction.
目的
成人心肌梗死的反应会导致炎症、疤痕形成、左心室扩张以及区域性和全球性功能丧失。胎儿真皮和肌腱的无疤痕再生愈合已得到证实，其炎症反应较轻。我们假设，在胎儿心肌梗死后，炎症反应会轻微，会出现再生性愈合，并保持功能。
方法
在成年或早期妊娠胎儿羊中创建前壁心肌梗死，涵盖左心室的 20%。使用定量超声心动图连续评估心肌功能。通过组织学检查梗死结构，观察疤痕形成的证据。使用免疫组织化学评估细胞炎症、细胞增殖和细胞凋亡。
结果
在成年羊心肌梗死后 4 周，射血分数（EF）显著下降（41±7.4%至 26±7.4%，p<0.05），并且无运动心肌节段增大（6.9±0.8cm 至 7.9±1.1cm，p<0.05）。相比之下，胎儿 EF 没有下降（53±8.1%至 55±8.8%），且在梗死后 4 周没有无运动胎儿心肌节段。与成人相比，胎儿梗死缺乏炎症细胞浸润，愈合后纤维化程度较低。胎儿梗死中也有 BrdU（5-溴-2'-脱氧尿苷）+增殖细胞，包括心肌细胞，位于梗死区内。
结论
这些数据表明，胎儿对心肌梗死的反应与成人有很大的不同，其特征是炎症反应轻微、缺乏纤维化、心肌增殖和心功能恢复。炎症反应减轻与胎儿受伤后再生性心脏愈合有关。了解胎儿心肌再生所涉及的机制可能会导致应用于改变成人心肌梗死后的反应。
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