Enteric Nervous System Impairment in Gastroschisis
Enteric Nervous System Impairment in Gastroschisis
复制标题
DOI：
10.1055/s-0032-1326955
复制
发表时间：
2013-02-01
影响因子：
1.8
通讯作者：
Audry, Georges
中科院分区：
文献类型：
--
作者：
Auber, Frederic;Danzer, Enrico;Audry, Georges
介绍腹裂手术修复后，大多数新生儿表现出严重的肠动力障碍。我们假设肠神经系统或Cajal间质细胞（ICC）网络的发育受损有助于腹裂肠动力受损。我们在大鼠腹裂模型中评估了这一假设。材料和方法在妊娠第18天，在全身麻醉下通过手术在大鼠胎儿中造成腹裂，并在第22天收获小肠。评估肠重/长（IW/L）比和小肠壁厚度。对标本进行苏木精-伊红染色或用神经元细胞（Hoxb 5）、神经胶质细胞（GFAP，S100）和ICC（c-kit）的特异性标记物进行免疫组织化学染色。肌间神经丛的成熟进行了形态学评估，并与假手术和对照胎儿进行了比较。肠肌间神经丛的发展阶段从1（成熟）到3（非常不成熟）与E16至E22对照fetus.Results标本相比，假手术或对照fetus. Results相比，腹裂与平均肠重/肠长（IW/L）比，平均厚度的总，肌肉，和粘膜下层的小肠壁的增加。肌间神经丛存在于腹裂胎儿的小肠中，但所有肌间神经丛均表现出异常成熟。因此，在腹裂胎仔中，55%与E19-E20胎仔的不成熟肌间神经丛相似，45%与E16-E18胎仔中观察到的非常不成熟的肠系膜神经丛相似。与假手术组和对照组相比，腹裂组的内脏切除小肠中ICC含量较少，通常表现出弱c-kit染色或异常圆形，无分支。Hoxb 5是肠神经母细胞和神经元前体细胞的标志物，在所有组的肌间神经丛中表达相似。S100或GFAP染色显示所有组的肌间神经丛内均存在胶质细胞。S100表达水平在所有组中相似。相比之下，GFAP的表达水平是较高的腹裂组比在假手术和control groups.Conclusion我们的研究结果表明，延迟成熟的肠神经系统结合受损的ICC网络的发展可能在很大程度上解释了肠动力障碍的新生儿腹裂。
Introduction After surgical repair of gastroschisis, most neonates exhibit severe intestinal dysmotility. We hypothesized that impaired development of the enteric nervous system or interstitial cells of Cajal (ICC) network contributes to impaired intestinal motility in gastroschisis. We evaluated this hypothesis in a rat model of gastroschisis.Material and Methods Gastroschisis was created surgically in rat fetuses on gestational day 18, under general anesthesia, and small bowel was harvested on day 22. Intestinal weight-to-length (IW/L) ratio, and small-bowel wall thickness were assessed. Specimens were processed for hematoxylin-eosin staining or immunohistochemistry with specific markers for neuronal cells (Hoxb5), glial cells (GFAP, S100), and ICCs (c-kit). Myenteric plexus maturation was assessed morphologically and compared with sham and control fetuses. Stage of development of the myenteric plexus was graded from 1 (mature) to 3 (very immature) comparatively with specimens from E16 to E22 control fetuses.Results Compared with sham-operated or control fetuses, gastroschisis was associated with increases in mean intestinal weight/intestinal length (IW/L) ratio, and mean thicknesses of the total, muscular, and submucosal layers of the small-bowel wall. The myenteric plexus were present in the small bowel from fetuses with gastroschisis, however all exhibited abnormal myenteric plexus maturation. Thus, of the gastroschisis fetuses, 55% had an aspect similar to the immature myenteric plexus of E19-E20 fetuses and 45% to the very immature mesenteric plexus observed in E16-E18 fetuses. When compared with sham and control groups, ICCs were less abundant in eviscerated small bowel in the gastroschisis group and often exhibited weak c-kit staining or an abnormally round shape without branches. Hoxb5, a marker for enteric neuroblasts and neuronal precursors, was expressed similarly in myenteric plexuses in all groups. S100 or GFAP staining showed the presence of glial cells within the myenteric plexuses in all groups. The S100 expression level was similar in all groups. In contrast, the GFAP expression level was higher in the gastroschisis group than in the sham and control groups.Conclusion Our results suggest that delayed maturation of the enteric nervous system combined with impaired ICC network development may largely explain the intestinal dysmotility seen in neonates with gastroschisis.