Innervation of the entire internal anal sphincter in a mouse model of Hirschsprung's disease: a first report.
Innervation of the entire internal anal sphincter in a mouse model of Hirschsprung's disease: a first report.
复制标题
先天性巨结肠症小鼠模型中整个肛门内括约肌的神经支配：第一份报告。
DOI：
10.1007/s00383-018-4397-z
复制
发表时间：
2019
影响因子：
1.8
通讯作者：
Yamataka A.
中科院分区：
文献类型：
--
作者：
Takeda M;Miyahara K;Sueyoshi R;Arakawa A;Lane GJ;Yamataka A.
背景先天性巨结肠（HD）患者术后排便障碍可能与肛门内括约肌（IAS）功能受损有关。虽然已经报告了HD中部分IAS的神经支配，但缺乏基于解剖标志的准确细节，这些细节可以解释POD中观察到的临床发病率，并且似乎没有研究专门记录HD中“整个”IAS的神经支配。我们使用内皮素受体B基因敲除小鼠代表HD（HD小鼠）和C57 B6野生小鼠作为对照（C小鼠），以调查整个IAS的神经支配，以评估病理生理学的POD experimental.MethodsThe纵向肌肉层的终点被用来定义IAS和环形肌肉层（CML）之间的边界。用PGP 9.5和S100作为一般神经标记物，nNOS和VIP作为副交感神经标记物，TH作为交感神经标记物，以及钙网膜蛋白作为HD的可靠诊断标记物对HD和C小鼠的肛门直肠标本进行免疫染色。结果在荧光显微镜下，与C小鼠相比，HD小鼠IAS中的PGP 9.5、nNOS和calretinin显著降低（分别为p< 0.05），而HD-小鼠和C-小鼠之间的S100，VIP，或TH。结论我们首次证实了神经支配的组织化学标记物在HD小鼠的整个IAS中的表达是异常的。这一发现的应用可能有利于防止POD，需要进一步研究。
BackgroundImpaired function of the internal anal sphincter (IAS) may be implicated in postoperative obstructed defecation (POD) that may complicate Hirschsprung’s disease (HD) patients. While innervation of part of the IAS in HD has been reported, accurate details based on anatomic landmarks that can explain the clinical morbidity seen in POD are lacking, and there appear to be no studies that specifically document the innervation of the “entire” IAS in HD. We used endothelin receptor-B knockout mice to represent HD (HD-mice) and C57B6 wild mice as controls (C-mice) to investigate the innervation of the entire IAS to assess the pathophysiology of POD experimentally.MethodsThe end-point of the longitudinal muscle layer was used to define the border between the IAS and the circular muscle layer (CML). Specimens of anorectum from HD- and C-mice were immunostained with PGP 9.5 and S100 as general nerve markers, nNOS and VIP as parasympathetic nerve markers, TH as a sympathetic nerve marker, and calretinin as a reliable diagnostic marker for HD. Immunostained cells/fibers were quantified using ImageJ.ResultsOn fluorescence microscopy, PGP 9.5, nNOS, and calretinin were significantly lower in the IAS of HD-mice than in C-mice (p< 0.05, respectively), while there were no significant differences between HD-mice and C-mice for S100, VIP, or TH.ConclusionWe are the first to confirm that the expression of histochemical markers of innervation is abnormal throughout the “entire” IAS in HD-mice. Application of this finding may be beneficial for preventing POD and requires further research.