【摘要】 目的　研究细胞外基质纤维连接蛋白 (fibronectin ,FN)mRNA在维生素A缺乏胎鼠发育异常心脏中的表达特征 ,探索FN在先天性心脏病分子水平发病机理中的作用及其意义。方法　采用地高辛标记探针原位杂交方法检测FNmRNA在时相、部位上的表达规律。研究对象分为维生素A缺乏胎鼠心脏畸形组 (实验组Ⅰ )、维生素A缺乏胎鼠心脏正常组 (实验组Ⅱ )和正常饲料喂食的对照胎鼠组进行对比 ,用MC 140 7DZ图象分析系统对杂交结果进行定量分析。结果　正常胎鼠FN于胎龄 11d主要分布于原始心管及心球的内膜。于胎龄 13d开始迁移到动脉干、心室肌小梁、心内膜垫 ,其表达强度明显高于室间隔等部位 (P <0 0 0 1)。实验组 (Ⅰ、Ⅱ )胎龄 11～ 15d的心脏内分布部位与对照组基本相似 ,但表达强度明显低于对照组 ,且表达延迟。实验组Ⅰ中的表达又显著低于实验组Ⅱ(P <0 0 5 )。心脏严重畸形的胎鼠中FN在缺损部位的间隔及房室瓣中的表达在胎龄后期比对照组相对增高。结论　纤维连接蛋白在心管融合及心内膜垫发育中起着重要的介导作用。维生素A缺乏对胚胎发育早、中期的胎鼠心脏FN剪切有影响 ,可导致FN表达减弱并延迟 ,维生素A缺乏是胎鼠先天性心脏病发生的机制之一。更多还原

【Abstract】 Objective Vitamin A deficiency (VAD) can cause cardiovascular malformations during early stage of fetal cardiac development. The possible mechanism is that VAD interferes with the expression of extra cellular matrix (ECM) and blocks the regulation of ECM on the pathway of cardiovascular pathogenesis. The aim of this study was to investigate the temporal expression of fibronectin (FN) mRNA during vitamin A deficiency rat embryonic heart development, and to explore the role of FN on the molecular pathogenesis of the congenital heart disease. Methods The Wistar rat embryos were divided into three groups: control group of rats with normal food, group I of VAD rats with cardiac malformation, and group Ⅱ of VAD rats with normal cardiac structure. In situ hybridization approach, by using the digoxigenin-labeled FN probe, was applied to detect FN spatiotemporal expressions from gestation day 11 to 19. The distribution of FN in different groups was analyzed by using MC-1407DZ image analysis system. Results In control group, no cardiovascular malformation was found. At embryonic day (ED) 11 the FN distribution was identified in endocardium of the primary cardiac tube and bulbus. There was a progressive increase in accumulation at ED13, FN was found mainly in the artery trunk (AT), trabeculae of ventricle (VT) and endocardial cushion (EC), where FN showed much more intensive expression than that in outflow (OFT), interventricular septum (IVS) and interatrial septum (IAS) (P<0.001). In group I and Ⅱ, the total detection rate of cardiovascular defects was 46.3%. The expression and distribution of FN mRNA in group I and Ⅱ showed weaker and delayed compared to that in control group. The FN expression was even lower in group I than that in group Ⅱ (P<0.05). In cardiac malformation rat embryos the FN showed a relatively higher expression at the malformed locations, such as IVS and atrioventricular valves, during the late gestational age (ED17-19) than that in control embryos. Conclusion FN might play an important mediation role in the fusion of primary cardiac tube and the development of endocardial cushion. VAD may affect the splicing of FN in the early and middle period of embryonic development from ED11 to ED15 in rats, and significantly decrease and delay the expression of FN. The abnormal expression of FN is most probably one of a pathogenesis of the congenital heart disease in VAD rat model.更多还原