論文

査読有り
2015年7月

Microangiopathy triggers, and inducible nitric oxide synthase exacerbates dextran sulfate sodium-induced colitis

LABORATORY INVESTIGATION
  • Hiroki Saijo
  • ,
  • Norifumi Tatsumi
  • ,
  • Seiji Arihiro
  • ,
  • Tomohiro Kato
  • ,
  • Masataka Okabe
  • ,
  • Hisao Tajiri
  • ,
  • Hisashi Hashimoto

95
7
開始ページ
728
終了ページ
748
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/labinvest.2015.60
出版者・発行元
NATURE PUBLISHING GROUP

Ulcerative colitis (UC) is a representative clinical manifestation of inflammatory bowel disease that causes chronic gastrointestinal tract inflammation. Dextran sulfate sodium (DSS)-induced colitis mice have been used to investigate UC pathogenesis, and in this UC model, disturbance and impairment of the mucosal epithelium have been reported to cause colitis. However, how DSS sporadically breaks down the epithelium remains unclear. In this study, we focused on the colonic microcirculation and myenteric neurons of DSS-induced colitis. Moreover, we examined the potential of myenteric neurons as a target to prevent exacerbation of colitis. Fluorescent angiographic and histopathological studies revealed that DSS administration elicited blood vessel disruption before epithelial disorders appeared. Ischemic conditions in the lamina propria induced inducible nitric oxide synthase (iNOS) expression in myenteric neurons as colitis aggravated. When neuronal activity was inhibited with butylscopolamine, neuronal iNOS expression decreased, and the exacerbation of colitis was prevented. These results suggested that DSS-induced colitis was triggered by microcirculatory disturbance in the mucosa, and that excessive neuronal excitation aggravated colitis. During remission periods of human UC, endoscopic inspection of the colonic microcirculation may enable the early detection of disease recurrence, and inhibition of neuronal iNOS expression may prevent the disease from worsening.

Web of Science ® 被引用回数 : 11

リンク情報
DOI
https://doi.org/10.1038/labinvest.2015.60
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25938626
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000357060000003&DestApp=WOS_CPL

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