Wedel T, Holschneider A M, Krammer H J
Department of Anatomy, Medical University of Lübeck, Germany.
Eur J Pediatr Surg. 1999 Apr;9(2):75-82. doi: 10.1055/s-2008-1072217.
Although the pathogenesis of Hirschsprung's disease (HD) is not completely resolved, both the absence of nerve cells and the hypertrophy of nerve fascicles within the aganglionic colonic segment have been attributed to an abnormal intestinal microenvironment. Studies on animal models for HD revealed an altered ultrastructure of ingrowing nerve fascicles and abnormalities of basal laminae (BL). Therefore, the purpose of this study was to examine the ultrastructure of hypertrophied nerve fascicles in human HD with special reference to structural abnormalities of BL. Colonic specimens were obtained from patients with HD (n = 10) and controls (n = 5) and processed for electron-microscopical examination. Hypertrophied nerve fascicles were characterized by a prominent perineural sheath surrounded by large amounts of collagen bundles, a collagen-filled endoneurium, vasa nervorum and abundant glial cells of extraenteric ultrastructure, which were arranged in mono- or oligoaxonal units and frequently displayed different stages of myelination. As these ultrastructural characteristics resembled typical features of extrinsic nerves and were similar to those observed in subserosal nerves, the prominent intramural nerve fascicles were considered to be of extraenteric origin. Most likely their overabundance contributes to the functional obstruction of the terminal colon. Morphological abnormalities of BL encountered in the aganglionic colonic segment consisted of an extensive multilamination of BL surrounding glial processes and an irregular thickening of BL surrounding perineurocytes and smooth muscle cells of the muscularis mucosae. Similar alterations in BL have also been described in inherited peripheral and diabetic autonomic neuropathies and attributed to reactivated schwann cells. Thus, the overproduction of BL material within the hypertrophied nerve fascicles in HD may reflect an increased activity of proliferating glial cells. Since the smooth muscle cells of the muscularis mucosae showed abnormalities of BL similar to those observed in murine models for HD, it is suggestive that also in human HD the aganglionic colon is affected by a disturbed intestinal micro-environment impairing the neuronal colonisation and promoting the ingrowth of extrinsic nerves. The ultrastructurally observed alterations in BL of both neuronal and non-neuronal cells, as well as the increased amount of perineural and endoneural collagen provide further evidence that extracellular matrix components are abnormally distributed and overproduced within the bowel wall of patients affected by HD.
尽管先天性巨结肠（HD）的发病机制尚未完全阐明，但无神经节结肠段内神经细胞的缺失和神经束的肥大均被归因于异常的肠道微环境。对HD动物模型的研究揭示了长入神经束超微结构的改变以及基膜（BL）的异常。因此，本研究的目的是特别参照BL的结构异常来检查人类HD中肥大神经束的超微结构。从HD患者（n = 10）和对照组（n = 5）获取结肠标本，并进行电子显微镜检查。肥大的神经束的特征是有一个由大量胶原束包围的明显神经周鞘、充满胶原的神经内膜、神经血管和具有肠外超微结构的丰富神经胶质细胞，这些细胞以单轴突或寡轴突单位排列，并经常显示出不同阶段的髓鞘形成。由于这些超微结构特征类似于外在神经的典型特征，并且与浆膜下神经中观察到的特征相似，因此突出的壁内神经束被认为起源于肠外。它们的过度增生很可能导致终末结肠的功能性梗阻。在无神经节结肠段中遇到的BL形态异常包括围绕神经胶质突起的BL广泛多层化以及围绕神经周细胞和黏膜肌层平滑肌细胞的BL不规则增厚。在遗传性周围神经病和糖尿病性自主神经病中也描述了BL的类似改变，并归因于雪旺细胞的重新激活。因此，HD中肥大神经束内BL物质的过度产生可能反映了增殖神经胶质细胞活性的增加。由于黏膜肌层的平滑肌细胞显示出与HD小鼠模型中观察到的类似的BL异常，这表明在人类HD中，无神经节结肠也受到肠道微环境紊乱的影响，这种紊乱损害了神经元的定植并促进了外在神经的长入。在神经元和非神经元细胞的BL中通过超微结构观察到的改变，以及神经周和神经内膜胶原量的增加，进一步证明了细胞外基质成分在HD患者肠壁内分布异常且过度产生。
