Parikh D H, Tam P K, Van Velzen D, Edgar D
Department of Child Health, Royal Liverpool Children's Hospital, England.
Gastroenterology. 1992 Apr;102(4 Pt 1):1236-41.
In vitro neurite outgrowth and neuronal survival are promoted by laminin, and neuronal migration is promoted by collagen type IV. This led to the hypothesis that Hirschsprung's disease (HD) could be the result of an abnormal extracellular matrix microenvironment in the affected bowel during embryogenesis. Using indirect immunohistochemistry, we studied the distribution of laminin and collagen type IV in the bowel specimens of eight HD patients (four neonates and four infants) and 16 age- and site-matched controls from non-HD patients. In eight HD specimens, the tissue studied was from the aganglionic, transitional, and proximal normoganglionic zones. Uniform distribution of laminin and collagen type IV was observed in the basement membranes of all control specimens. The semiquantitative abnormality in the distribution of these proteins in HD occurred as follows: immunoreactivities were more intense in the inner circular layer, diminishing with a gradient in the outer muscularis externa in six of six aganglionic, four of five transitional, and three of eight normoganglionic sections. The qualitative abnormality of these proteins in HD was speckled immunofluorescence outside the basement membranes of the muscularis externa in all three zones of neonatal specimens only. These findings support the microenvironment hypothesis of the pathogenesis of HD.
层粘连蛋白可促进体外神经突生长和神经元存活，IV型胶原可促进神经元迁移。由此产生了一种假说，即先天性巨结肠病（HD）可能是胚胎发育过程中受累肠段细胞外基质微环境异常所致。我们采用间接免疫组织化学方法，研究了8例HD患者（4例新生儿和4例婴儿）以及16例年龄和部位匹配的非HD患者对照的肠标本中层粘连蛋白和IV型胶原的分布情况。在8例HD标本中，研究的组织来自无神经节区、移行区和近端正常神经节区。在所有对照标本的基底膜中均观察到层粘连蛋白和IV型胶原的均匀分布。HD中这些蛋白分布的半定量异常情况如下：在6例无神经节区标本中的6例、5例移行区标本中的4例以及8例正常神经节区标本中的3例中，免疫反应在内环层更强烈，在外肌层中呈梯度减弱。仅在新生儿标本的所有三个区域中，这些蛋白在HD中的定性异常表现为外肌层基底膜外的斑点状免疫荧光。这些发现支持了HD发病机制的微环境假说。
