大鼠肛门直肠畸形的胚胎发育研究

目的：观察大鼠正常的和畸形的肛门直肠发育过程，探讨肛门直肠畸形的胚胎发生机制。方法：用乙烯硫脲（ethylenethiourea,ETU）致畸21只孕鼠共生产泄殖腔畸形和无肛畸形胎鼠（204只）。胎龄12．5－20d的正常（n=223)及泄殖腔发育畸形的胎鼠正中矢状连续切片HE染色。连续动态对比观察泄殖腔及肛门直肠的发育过程。结果：泄殖腔发育过程中，胎龄15d前的正常鼠胚，尿直肠隔将泄殖分为腹侧的尿生殖窦和背侧的直肠两部分，二者共同相通于泄殖腔管，尿直肠隔下降与泄殖腔膜的距离逐渐减小，直至胚胎15d时与泄殖腔膜融合，直肠与膀胱分离。16d时肛膜破裂，直肠与尾沟相通。ETU致畸的胎鼠泄殖腔发育中有以下下特点；（1）尿直肠隔始终未与泄殖腔膜融合；（2）泄殖腔构型异常；（3）泄殖腔膜过短；（4）没有尾沟形成。ETU致畸胎鼠中所有的无肛畸形均为泄殖腔畸形和直肠尿道瘘。结论：鼠胚胎15d时尿直肠隔与泄殖腔膜融合。胚胎16d肛膜完全破裂，直肠与外界相通。泄殖腔构型的变化以及尿直肠隔下降并与泄殖腔隔合使直肠与膀胱分离。尿直肠隔与泄殖腔膜融合是直肠和膀胱分离的决定因素。肛门直肠畸形发生与泄殖腔构型异常以及尿直肠隔未与泄殖腔膜融合等因素有关。尿直肠隔未与泄殖腔融合是ETU诱导的大鼠肛门直肠畸形发生的直接原因。

Development of anorectal malformation in murine fetal models

Objective To study the development of anorectal malformation (ARM) in rats. Methods Rat embryos with ARM were generated by administration of ethylenethiourea (ETU) to pregnant mice ( n =21). Normal rat embryos ( n =223) and embryos with ARM ( n =204) from gestational days 12.5 to 20 were serial sectioned sagittally and stained with HE. Temporo spatial study was carried out on cloaca and urorectal septum. Results In normal fetus, the urorectal septum (URS) descended, its distance to cloacal membrane decreased gradually. URS fused with cloacal membrane on gestational days 15 and hence separated of the future rectum dorsally and urogenital sinus ventrally. On gestational days 16, anal membrane broke down and the rectum communicated with the anus. The characteristics of cloaca development in ETU ARM rat embryos were as follows: 1.URS never fused with cloaca membrane, 2. Cloacal configuration was abnormal, 3. Cloacal membrane was too short and 4. Tail groove never appeared. All of the embryo rats with ARM developed rectourethal fistula and rectocloacal fistula. Conclusions In the normal rats on gestational days 15, URS fuses with cloacal membrane, and on gestational days 16 anal membrane ruptures and rectum communicate with the anus. The fusion of URS with cloacal membrane is essential to the separation of rectum from bladder. Occurrence of ARM is related to the abnormal cloaca formation. The failure of fusion of URS with cloacal membrane leads to ARM in ETU rat models.