Disruption of the pacemaker activity of interstitial cells of Cajal via nitric oxide contributes to postoperative ileus
Disruption of the pacemaker activity of interstitial cells of Cajal via nitric oxide contributes to postoperative ileus
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DOI：
10.1111/nmo.13334
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发表时间：
2018-08-01
影响因子：
3.5
通讯作者：
Hori, M.
中科院分区：
文献类型：
--
作者：
Kaji, N.;Nakayama, S.;Hori, M.
背景Cajal间质细胞（interstitial cells of Cajal，ICC）是肠道起搏器。术后肠梗阻（Postoperative ileus，POI）是腹部手术后发生的一种胃肠动力障碍性疾病，是由炎症引起的平滑肌和肠神经元功能障碍引起的。然而，ICC在POI中的参与并不为人所知。在这项研究中，我们研究了ICC的功能变化，在小鼠模型的POI。Methodsintestinal manipulation（IM）进行诱导POI。分别于IM后24 h和48 h测定肠图尼卡肌层的场电位。组织也通过免疫组织化学和电子显微镜analysis.Key Results胃肠传输显着减少肠图尼卡肌层炎症后24小时IM，这是改善IM后48小时。IM后24 h起搏电位的产生和传播中断，48 h恢复到对照水平。ICC网络，检测c-Kit免疫反应，在IM后24小时显着中断。电子显微镜分析显示ICC细胞质中存在异常空泡。有趣的是，ICC网络在IM后48小时恢复。氨基胍，一种诱导型一氧化氮合酶抑制剂的管理，抑制了ICC网络的破坏。回肠平滑肌组织培养的存在下，一氧化氮供体，显示中断ICC networks.Conclusions和InferencesThe产生和传播的起搏电位ICC中断通过一氧化氮IM后，这种中断可能有助于POI。当炎症减轻时，ICC可恢复其起搏功能。
BackgroundInterstitial cells of Cajal (ICC) serve as intestinal pacemakers. Postoperative ileus (POI) is a gastrointestinal motility disorder that occurs following abdominal surgery, which is caused by inflammation-induced dysfunction of smooth muscles and enteric neurons. However, the participation of ICC in POI is not well understood. In this study, we investigated the functional changes of ICC in a mouse model of POI.MethodsIntestinal manipulation (IM) was performed to induce POI. At 24h or 48h after IM, the field potential of the intestinal tunica muscularis was investigated. Tissues were also examined by immunohistochemistry and electron microscopic analysis.Key ResultsGastrointestinal transit was significantly decreased with intestinal tunica muscularis inflammation at 24h after IM, which was ameliorated at 48h after IM. The generation and propagation of pacemaker potentials were disrupted at 24h after IM and recovered to the control level at 48h after IM. ICC networks, detected by c-Kit immunoreactivity, were remarkably disrupted at 24h after IM. Electron microscopic analysis revealed abnormal vacuoles in the ICC cytoplasm. Interestingly, the ICC networks recovered at 48h after IM. Administration of aminoguanidine, an inducible nitric oxide synthase inhibitor, suppressed the disruption of ICC networks. Ileal smooth muscle tissue cultured in the presence of nitric oxide donor, showed disrupted ICC networks.Conclusions and InferencesThe generation and propagation of pacemaker potentials by ICC are disrupted via nitric oxide after IM, and this disruption may contribute to POI. When inflammation is ameliorated, ICC can recover their pacemaker function.