Srinathan S K, Langer J C, Botney M D, Pelletier G J
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Surg Res. 1996 Sep;65(1):25-30. doi: 10.1006/jsre.1996.0338.
Gastroschisis is a congenital anomaly in which the intestines are exposed to amniotic fluid throughout fetal life. Previous studies in animal models have demonstrated smooth muscle thickening and decreased contractility, epithelial dysfunction, and submucosal thickening. The present studies were done to further define the mechanism of submucosal changes by investigating collagen deposition and gene expression in a rabbit model. Gastroschisis was surgically created in fetal rabbits at 24 days gestation (term is 31 days). Sham-operated and unoperated fetuses served as controls. Fetuses were sacrificed and bowels were harvested at 26, 28, and 31 days gestation. Animal weight and gross and histologic appearance were assessed. Submucosal collagen content was measured using the van Geison stain. In situ hybridization of the expression of alpha (1) procollagen RNA was done to determine the distribution and source of submucosal collagen. At term, submucosal thickening was present in animals with gastroschisis, associated with a significantly increased collagen content. Collagen distribution was also more diffuse in the gastroschisis animals than in controls. In situ hybridization revealed procollagen expression in round cells located in the submucosa and not in smooth muscle. These cells did not resemble fibroblasts, and their identity is uncertain. Experimental gastroschisis is characterized by submucosal thickening which is associated with changes in collagen, including increased deposition and more diffuse distribution in the submucosa. The cells responsible for production of procollagen are round, nonfibroblast cells which are located in the submucosa and not in the smooth muscle layer. These findings may have some importance in understanding the mechanisms responsible for intestinal malfunction in infants with gastroschisis.
腹裂是一种先天性畸形，在胎儿期肠道一直暴露于羊水中。以往在动物模型中的研究已表明存在平滑肌增厚和收缩性降低、上皮功能障碍以及黏膜下增厚。本研究旨在通过调查兔模型中的胶原蛋白沉积和基因表达来进一步明确黏膜下变化的机制。在妊娠24天（足月为31天）时通过手术制造兔胎儿腹裂模型。假手术和未手术的胎儿作为对照。在妊娠26、28和31天时处死胎儿并采集肠道。评估动物体重、大体外观和组织学表现。使用凡吉森染色法测量黏膜下胶原蛋白含量。进行α(1)前胶原RNA表达的原位杂交以确定黏膜下胶原蛋白的分布和来源。足月时，腹裂动物存在黏膜下增厚，伴有胶原蛋白含量显著增加。与对照相比，腹裂动物中的胶原蛋白分布也更弥散。原位杂交显示前胶原在位于黏膜下而非平滑肌中的圆形细胞中表达。这些细胞不像成纤维细胞，其身份尚不确定。实验性腹裂的特征是黏膜下增厚，这与胶原蛋白的变化有关，包括黏膜下沉积增加和分布更弥散。负责产生前胶原的细胞是位于黏膜下而非平滑肌层的圆形非成纤维细胞。这些发现对于理解腹裂婴儿肠道功能障碍的机制可能具有一定重要性。
