過敏性腸症候群における感作現象の役割と病態メカニズムの解明

阐明致敏现象和病理机制在肠易激综合征中的作用

• 批准号: 17659200
• 负责人: 中谷 久美
• 金额: $ 1.47万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Exploratory Research
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17659200/
• 关键词: ストレス; 心身医学; 消化器; CRH; 感作

【目的】平成17年度に採取した脳と腸を用いて以下の項目を検討し、感作現象におけるCRH receptor 1 (CRHR1)の役割および過敏性腸症候群(IBS)発症のメカニズムを明らかにする。1.大腸粘膜の炎症を好中球数、好酸球数、リンパ球数を指標とし、HE染色法にて検討する。2.脳及び大腸のCRHR1 mRNA発現を免疫組織化学染色法にて検討する。【対象】Wistar rat♂、6週齢、各群6匹【方法】trinitrobenzamine sulfonic acid (TNBS)を用い大腸に炎症を起こす。TNBSまたはvehicleを腸内に投与した後、6週間のリカバリー期間を置き、大腸の伸展刺激(80mmHg,20min/day)を6日間連続して行う。CRHR1拮抗薬としてCP-154,526を用い、伸展刺激前に投与する。6日目は、大腸伸展刺激の30分後に断頭し、脳・大腸を摘出する。【結果】大腸粘膜固有層の好中球数は、コントロール群に比し慢性内臓刺激群で有意に多く、炎症+慢性内臓刺激群及びCRHR1拮抗薬群では慢性内臓刺激群に比し有意に少なかった。また、大腸粘膜固有層の好酸球数は、慢性内臓刺激群に比し炎症+慢性内臓刺激群及びCRHR1拮抗薬群で有意に少なかった。大腸上皮内リンパ球数は、コントロール群に比し慢性内臓刺激群、炎症+慢性内臓刺激群及びCRHR1拮抗薬群で有意に多かった。大腸粘膜固有層の好中球数は、コントロール群に比し慢性内臓刺激群で有意に多く、炎症+慢性内臓刺激群及びCRHR1拮抗薬群では慢性内臓刺激群に比し有意に少なかった。【結論】繰り返しの消化管刺激が大腸粘膜の炎症反応を惹起し、この炎症による感作現象がIBSの発症と関与している可能性が示唆された。CRHR1の役割に関しては、今後、脳及び大腸のCRHR1 mRNA発現を更に検証する必要がある。

[Objective] The following items were taken in the fiscal year 2017 to investigate and clarify the role of CRH receptor 1 (CRHR1) and irritable bowel syndrome (IBS). 1. Inflammation of the large intestine mucosa was examined by HE staining, including the number of fine nodules, the number of fine nodules and the number of fine nodules. 2. Expression of CRHR1 mRNA in the colon and colon was examined by immunohistochemical staining. Wistar rat, 6 weeks old, 6 animals in each group TNBS was administered intramuscularly for 6 weeks, followed by colonic stretch stimulation (80mmHg,20min/day) for 6 days. CRHR1 antagonist CP-154,526 is administered before stretching stimulation. On the 6th, after 30 minutes of eye and large intestine stretching stimulation, the head was cut off and the large intestine was extracted. [Results] The number of good mitochondria in the lamina propria of the colon mucosa was significantly higher than that in the chronic internal stimuli group, and the number of inflammation + chronic internal stimuli group and CRHR1 antagonist group was significantly lower than that in the chronic internal stimuli group. In addition, the number of oxytocin in the lamina propria of the large intestine, chronic internal stimuli, inflammation + chronic internal stimuli, and CRHR1 antagonists are intentionally reduced. Colorectal epithelial cell number, cell group, chronic endocrine stimulation group, inflammation + chronic endocrine stimulation group, and CRHR1 antagonist group are intentionally increased. In the lamina propria of the large intestine, the number of good neurons is higher than that of chronic endocrine stimulation group, inflammation + chronic endocrine stimulation group and CRHR1 antagonist group, and the number of chronic endocrine stimulation group is lower than that of chronic endocrine stimulation group. [Conclusion] Irritation of digestive tract may cause inflammation of large intestine mucosa, and may be related to the development of IBS. CRHR1 gene expression is essential for further detection of CRHR1 gene expression in the future.

项目成果

Corticotropin-releasing Hormone Receptor 1 Antagoinist Blocks Brain-Gut Activation Induced by Colonic Distention in Rats.

促肾上腺皮质激素释放激素受体 1 拮抗剂可阻断大鼠结肠扩张引起的脑肠激活。

• 发表时间: 2005
• 期刊: Gastroenterology 129
• 作者: K Saito;T Kasai;Y Nagura;H Ito;M Kanazawa;S Fukudo.
• 通讯作者: S Fukudo.