权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Regulation of GI motility by cross-talk with nerve, pace maker anti immune cells

通过与神经、起搏器抗免疫细胞的串扰调节胃肠道运动

基本信息

批准号：
13306023
负责人：
HORI Masatoshi
金额：
$ 35.61万
依托单位：
THE UNIVERSITY OF TOKYO
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13306023/
关键词：
macrophage gut motility inflammation prostaglandins smooth muscle contraction nitric oxide IL-1β NOD2 腸

项目摘要

Intestinal motility is under the control of several systems, including the neurogenic, myogenic and endocrine systems. Morphological and functional studies in recent years have suggested that interstitial cells of Cajal (ICCs) are pacemakers in the musculature of the gastrointestinal tract. ICCs are arranged in distinctive patterns in close relation to nerve and smooth muscle cells in the muscle layer, and generate pacemaker currents to develop electrical slow waves in the gastrointestinal smooth muscles. In addition, muscularis resident macrophages are regularly distributed in the subserosa and at the level of the myenteric plexus. However, it remains to be determined how these cells coordinately contribute to the GI motility. In this study, we have obtained the following results :1)Inhibition of spontaneous contractions and peristalsis in circular smooth muscle from the colons of Crohn's disease model (TNBS-treated) rats is attributable to the impairment of ICCs and myenteric nerve systems. The indication of macrophage activation and the close correlation between the degeneration and macrophage accumulation suggest that the macrophages play critical a role in the degenerative pathology of intestinal motility.2)Decrease in the contraction of circular smooth muscle isolated from TNBS induced colitis rat colon is attributable to the decreased activity of the L type Ca-channel. The dysfunction of the L type Ca-channel may be mediated by NF-κB-dependent pathways.3)Treatment, of smooth muscle with IL-1□, which is derived mainly from macrophages, decreases either CPI-17 expression or MYPT I phosphorylation, which results in an increase in myosin phosphatase activity to reduce force generation. IL-1□ could be an important mediator of gastrointestinal motility disorders in IBD, etc.

肠蠕动受多个系统的控制，包括神经源性、肌源性和内分泌系统。近年来的形态学和功能研究表明，卡哈尔间质细胞（ICC）是胃肠道肌肉组织中的起搏器。 ICC 以独特的模式排列，与肌肉层的神经和平滑肌细胞密切相关，并产生起搏器电流，在胃肠道平滑肌中产生电慢波。此外，肌层巨噬细胞有规律地分布在浆膜下层和肌间神经丛水平。然而，这些细胞如何协调地促进胃肠道运动仍有待确定。在本研究中，我们获得了以下结果：1）克罗恩病模型（TNBS处理）大鼠结肠环形平滑肌自发收缩和蠕动的抑制归因于ICC和肌间神经系统的损伤。巨噬细L型Ca通道的功能障碍可能是由NF-κB依赖性途径介导的。3)用主要来源于巨噬细胞的IL-1□治疗平滑肌，可降低CPI-17表达或MYPT I磷酸化，从而导致肌球蛋白磷酸酶活性增加，从而减少力的产生。 IL-1□可能是IBD等胃肠道运动障碍的重要介质。