過敏性腸症候群の内臓知覚過敏に関する研究

肠易激综合征内脏超敏反应的研究

• 批准号: 16F16753
• 负责人: 福土 審
• 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 JSPS Fellows
• 财政年份: 2016
• 资助国家: 日本
• 起止时间: 2016-11-07 至 2019-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16F16753/
• 关键词: 内臓知覚; 内臓知覚過敏; CRH; CRF; CRH受容体1; 過敏性腸症候群; 腹壁筋電図; 不安行動; ストレス; 大腸運動; 不安; 動物実験; 5-hydroxytryptamine; 内臓痛; 脳腸相関; 神経伝達物質; 動物モデル

Aim: Corticotropin-releasing hormone (CRH) and its receptors play important roles in colonic response to stress. We tested the hypothesis that peripheral CRH receptor 1 (CRH-R1) activation induces colonic visceromotor dysfunction as well as anxiety behavio. Methods: Male Wistar rats were divided into four groups. Either vehicle or CRH-R1 antagonist (CP-154,526) was injected subcutaneously 30 min before intraperitoneal injection of CRH-R1 agonist cortagine or vehicle. Colorectal distention (CRD) was performed two times over 20 minutes. The electromyogram (EMG) was recorded to measure the visceromotor responses (VMR) to CRD. Anxiety-related behavior was measured for 5 minutes during exposure to an elevated-plus maze (EPM). Results: Compared with vehicle, cortagine significantly induced increase in fecal pellets number (P < 0.05). CP-154,526 abolished the cortagine-induced fecal pellets output (P < 0.05). The amplitude of EMG has significant differences among four groups (P < 0.01). In the rats treated with cortagine, EMG amplitude was significantly higher than that control and CP group (P < 0.05). CP-154,526 has significantly decreased amplitude, compared with cortagine group (P < 0.05). The total travel distance in the EPM has significantly differences among four groups (P = 0.01). Conclusions: Our results suggest that peripheral cortagine injection can stimulate defecation and induce visceral hypersensitivity in rats, which were abolished by CRH-R1 antagonist. Peripheral cortagine may induce anxiety-related behaviour while CRH-R1 antagonist reduces the anxiety behavior.

目的：促肾上腺皮质激素释放激素（CRH）及其受体在结肠应激反应中起重要作用。我们验证了外周CRH受体1 （CRH- r1）激活诱导结肠脏器运动功能障碍和焦虑行为的假设。方法：雄性Wistar大鼠分为4组。在腹腔注射CRH-R1激动剂cortagine或载体前30分钟皮下注射载体或CRH-R1拮抗剂（CP-154,526）。结肠膨胀（CRD）在20分钟内进行两次。记录肌电图（electromyogram， EMG）来测量内脏运动对CRD的反应（VMR）。在暴露于升高迷宫（EPM）期间，测量焦虑相关行为5分钟。结果：与对照组相比，可他汀显著诱导大鼠粪球数量增加（P < 0.05）。CP-154,526抑制了cortagin诱导的粪丸量（P < 0.05）。四组间肌电图幅值差异有统计学意义（P < 0.01）。cortagine组大鼠肌电波幅显著高于对照组和CP组（P < 0.05）。与cortagine组相比，CP-154,526的振幅显著降低（P < 0.05）。EPM总行程在四组间差异有统计学意义（P = 0.01）。结论：外周注射cortagine可刺激大鼠排便，诱导内脏超敏反应，而CRH-R1拮抗剂可消除这一作用。外周药可诱导焦虑相关行为，而CRH-R1拮抗剂可降低焦虑相关行为。

项目成果

東北大学病院心療内科

东北大学医院心身医学科

China-Japan Friendship Hospital/Peking Union Medical College(中国)

中日友好医院/北京协和医学院（中国）

Lecture: Impact of stress on brain-gut interactions in irritable bowel syndrome.

讲座：压力对肠易激综合征脑肠相互作用的影响。

• 发表时间: 2018
• 作者: Yanli Zhang;Emiko Tsuchiya;Hiromichi Tsushima;Tomohiko Muratsubaki;Motoyori Kanazawa;Shin Fukudo.;Shin Fukudo.
• 通讯作者: Shin Fukudo.

China-Japan Friendship Hospital(China)

中日友好医院（中国）

Effects of corticotropin-releasing hormone receptor 1 antagonist on colonic sensorimotor dysfunction and emotional responses in rats.

促肾上腺皮质激素释放激素受体 1 拮抗剂对大鼠结肠感觉运动功能障碍和情绪反应的影响。

• 发表时间: 2018
• 作者: Yanli Zhang;Emiko Tsuchiya;Hiromichi Tsushima;Tomohiko Muratsubaki;Motoyori Kanazawa;Shin Fukudo.
• 通讯作者: Shin Fukudo.