Mechanisms of the gastrointestinal motility dysfunction under septic conditions - a role of Interstitial Cells of Cajal -

脓毒症条件下胃肠动力功能障碍的机制 - 卡哈尔间质细胞的作用 -

基本信息

批准号：
11557093
负责人：
NISHIDA Toshirou
金额：
$ 8.13万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11557093/
关键词：
Intestinal motility Endotoxin Interstitial Cells of Cajal Macrophage nitric oxide iNOS Infection KIT

项目摘要

Patients with severe sepsis frequently accompany gastrointestinal dysfunction such as paralytic ileus. The latter is thought to induce bacterial translocation, which may aggravate septic states of the patients. The mechanism of gastrointestinal motor dysfunction, however, is still unknown. Interstitial cells of Cajal (ICC) generate electric slow wave and thus are considered gastrointestinal pacemaker cells. We have investigated the mechanism of ICC injury under septic conditions using lipopolysaccharide (LPS)-injection model of mouse. Intraperitoneal injection of LPS decreased spontaneous intestinal movement, dose- and time- dependently. Similar results were obtained by measuring electric activity of electric slow wave. LPS also induced activation of macrophages and induction of iNOS in them. i.p. injection of LPS also caused decrease in KIT-positive cells in and around the myenteric plexus, LPS-induced decrease in both spontaneous intestinal movement and the KIT-positive cell number was restored by pretreatment of Gadlinium and addition of iNOS inhibitors. The additions of NO releaser, FK409, caused abrupt decrease in spontaneous intestinal movement in vitro. In vivo addition of FK409 caused decrease in both spontaneous intestinal movement and the KIT-positive cell number. The present results indicate that NO produced by iNOS, which is induced in activated macrophages by LPS, caused ICC injury, resulting in decrease in spontaneous intestinal movement and thus LPS-induced intestinal dysfunction.

严重败血症的患者经常伴有胃肠道功能障碍，例如麻痹性肠胃疾病。后者被认为会诱导细菌易位，这可能会加剧患者的败血性状态。然而，胃肠道功能障碍的机制仍然未知。 Cajal（ICC）的间质细胞会产生电慢波，因此被认为是胃肠道起搏器细胞。我们已经使用小鼠的脂多糖（LPS）注射模型研究了ICC损伤的机制。腹膜内注射LPS会降低自发性肠道运动，剂量和时间依赖。通过测量电慢波的电活动获得了类似的结果。 LP还诱导了巨噬细胞的激活和iNOS的诱导。 I.P.注射LPS还导致肌丛中和周围的Kit阳性细胞的减少，LPS诱导的自发性肠道运动均降低，并且通过预处理Gadlinium和添加Inos抑制剂，可以恢复KIT阳性细胞数量。无释放器FK409的添加导致体外自发肠道运动的突然降低。体内添加FK409导致自发肠道运动和试剂盒阳性细胞数的减少。目前的结果表明，INOS产生的NO（由LPS激活的巨噬细胞诱导）导致ICC损伤，从而导致自发性肠道运动的降低，从而导致LPS诱导的肠道功能障碍。