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Alterations in the distal colon innervation in Winnie mouse model of spontaneous chronic colitis

机译:Winnie小鼠自发性慢性结肠炎模型中远端结肠神经支配的改变

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The gastrointestinal tract is innervated by extrinsic sympathetic, parasympathetic and sensory nerve fibers as well as by intrinsic fibers from the neurons in myenteric and submucosal ganglia embedded into the gastrointestinal wall. Morphological and functional studies of intestinal innervation in animal models are important for understanding the pathophysiology of inflammatory bowel disease (IBD). The recently established Winnie mouse model of spontaneous chronic colitis caused by a point mutation in the Muc2 mucin gene develops inflammation due to a primary epithelial defect. Winnie mice display symptoms of diarrhea, ulcerations and rectal bleeding similar to those in IBD. In this study, we investigated myenteric neurons, noradrenergic, cholinergic and sensory nerve fibers in the distal colon of Winnie (Win/Win) mice compared to C57/BL6 and heterozygote littermates (Win/Wt) using histological and immunohistochemical methods. All Win/Win mice used in this study had inflammation with signs of mucosal damage, goblet cell loss, thickening of muscle and mucosal layers, and increased CD45-immunoreactivity in the distal colon. The density of sensory, cholinergic and noradrenergic fibers innervating the myenteric plexus, muscle and mucosa significantly decreased in the distal colon of Win/Win mice compared to C57/BL6 and Win/Wt mice, while the total number of myenteric neurons as well as subpopulations of cholinergic and nitrergic neurons remained unchanged. In conclusion, changes in the colon morphology and innervation found in Winnie mice have multiple similarities with changes observed in patients with ulcerative colitis.
机译:肠胃道由外在交感神经,副交感神经和感觉神经纤维以及埋入胃肠道壁的肌层和粘膜下神经节中神经元的固有纤维神经支配。在动物模型中进行肠道神经支配的形态学和功能研究对于理解炎症性肠病(IBD)的病理生理至关重要。最近建立的由Muc2粘蛋白基因中的点突变引起的自发性慢性结肠炎的Winnie小鼠模型由于原发性上皮缺陷而发炎。小熊小鼠表现出腹泻,溃疡和直肠出血的症状,类似于IBD。在这项研究中,我们使用组织学和免疫组化方法研究了Winnie(Win / Win)小鼠远端结肠与C57 / BL6和杂合子同窝仔(Win / Wt)的肌层神经元,去甲肾上腺素能,胆碱能和感觉神经纤维。在这项研究中使用的所有Win / Win小鼠都有炎症反应,有粘膜损伤,杯状细胞丢失,肌肉和粘膜层增厚的迹象,并且远端结肠的CD45免疫反应性增加。与C57 / BL6和Win / Wt小鼠相比,Win / Win小鼠远端结肠中支配肌层神经丛,肌肉和粘膜的感觉,胆碱能和去甲肾上腺素能纤维的密度显着降低,而肌层神经元和亚群的总数胆碱能和硝酸能神经元的数量保持不变。总之,在Winnie小鼠中发现的结肠形态和神经支配变化与溃疡性结肠炎患者的观察到的变化具有多种相似性。

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