Developmental defects of coronary vasculature in rat embryos administered bis-diamine and WKY/NCrj rat embryos

1.在妊娠10.5天时，对妊娠Wister大鼠单次给予200 mg双二胺。对10只母鼠的52只胚胎进行冠状动脉形态学分析。结果：1. 52例胚胎中有48例出现圆锥动脉干异常，均为左冠状动脉发育不全或发育不良.首次在胚胎14.5天（艾德）对照大鼠胚胎的心脏中检测到冠状血管。然而，在双二胺处理的胚胎中，在艾德14.5、15.5、16.5和17.5的ED下，显示出对心外膜-内皮转化的不良促进，导致冠状血管的异常发育。V-CAM和tenascine在冠状动脉内皮细胞中表达较少。窦状隙在较薄的心室壁内广泛而深入.使用全胚胎培养物对早期双二胺处理的大鼠胚胎进行发育分析，发现在干分裂前流出道明显延长，心室扩大，心肌壁变薄。组织学检查未发现冠状动脉芽，动脉主干周围有稀疏的N-CAM阳性细胞。这也是早期WKY/NCrj大鼠胚胎的情况。当双二胺给药于妊娠10、11和12天的母鼠时，分别在0%、93%和32%的胚胎中观察到异常圆锥干分裂。此外，只有在妊娠第11和12天给予双二胺时才发现异常冠状动脉，其发生率与异常干细胞分裂的发生率相一致，虽然不能明确神经嵴细胞是否在冠状动脉芽形成中起作用，但这些研究表明，异常干细胞分裂和心包发育导致异常冠状动脉血管的形成和分布。

1. A single 200-mg dose of bis-diamine was administered to pregnant Wister rats at 10.5 days of gestation. Fifty-two embryos from 10 mother rats underwent morphological analysis of the coronary arteries. Conotruncal anomalies were detected in 48 of 52 embryos, and an aplastic or hypoplastic left coronary artery was found in all of them.2. Coronary vasculature was first detected in the heart of at 14.5 embryonic day (ED) control rat embryo. However, in the herats of bis-diamine treated embryos, poor promotion of epicardial-endothelial transformation was revealed at ED 14.5, 15.5,16.5, and 17.5, causing abnormal development of the coronary vasculature. V-CAM and tenascine were less expressed in the coronary vascular endothelial cells. Sinusoids were widely and deeply extended in the thin ventricular wall.3. Developmental analysis of the early bis-diamine treated rat embryos using whole embryo culture, disclosed a markedly elongated outflow tract and enlarged ventricle with thin myocardial wall before the truncal division. Histological examinations detected no coronary buds and sparse N-CAM positive cells around the arterial trunk. This was also the case with the early WKY/NCrj rat embryos.4. When bis-diamine was administered to the 10, 11, and 12 pregnant day mother rats, abnormal conotruncal division was seen in 0%, 93%, and 32% of the embryos, respectively. Furthermore, anomalous coronary arteries were detected only when bis-diamine was administered on 11 and 12 pregnant day, and the incidence was coincident with that of anomalous truncal division.Although not being able to clarify whether neural crest cells play a role in coronary bud formation, these studies suggested that abnormal truncal division and pericardial development caused anomalous coronary vascular formation and distribution.