Tam P K, Lister J
Gastroenterology. 1986 Jun;90(6):1901-6. doi: 10.1016/0016-5085(86)90259-3.
The most widely held view on the pathogenesis of Hirschsprung's disease as an arrest of neuroblast migration in the gut was based on the hypothesis of a single craniocaudal gradient of development of enteric neurons. Recent experimental studies in animals, however, have revived a contradictory hypothesis of a dual gradient of neuronal development; such data are not available in humans. To test these hypotheses in humans, we studied the pylorus, ileum, and colon of 28 fetuses with gestational ages of 9-21 wk, using immunohistochemical localization of neuron-specific enolase, a specific neuronal marker indicative of differentiation. Development of the enteric nervous system was shown to be most advanced in the pylorus, less so in the colon, and least so in the ileum. The findings support the hypothesis of a dual gradient of neuronal development proceeding from both ends to the middle of the gut in midtrimester human fetuses and suggest that the pathogenesis of Hirschsprung's disease needs to be reconsidered.
关于先天性巨结肠病发病机制的最普遍观点，即肠神经母细胞迁移在肠道中停滞，是基于肠神经元发育存在单一头尾梯度的假说。然而，最近动物实验研究重新提出了神经元发育双梯度的矛盾假说；此类数据在人类中尚无。为了在人类中验证这些假说，我们使用神经元特异性烯醇化酶（一种指示分化的特异性神经元标志物）的免疫组化定位，研究了28例孕龄为9至21周胎儿的幽门、回肠和结肠。结果显示，肠神经系统的发育在幽门最为先进，在结肠次之，在回肠最不发达。这些发现支持了妊娠中期人类胎儿肠道神经元发育从两端向中间进行双梯度的假说，并表明先天性巨结肠病的发病机制需要重新考虑。
