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：皮质激素释放激素（CRH）及其受体在结肠对胁迫的反应中起着重要作用。 我们检验了外围CRH受体1（CRH-R1）激活的假设可引起结肠内脏功能障碍以及焦虑行为。方法：雄性Wistar大鼠分为四组。在腹膜内注射CRH-R1激动剂Cortagine或媒介物之前，对媒介物或CRH-R1拮抗剂（CP-154,526）进行皮下注射30分钟。在20分钟内进行了两次结直肠扩张（CRD）。记录肌电图（EMG）以测量内脏运动反应（VMR）对CRD。在暴露于升高的迷宫（EPM）期间，测量与焦虑相关的行为5分钟。结果：与媒介物相比，皮质线显着诱导了粪便颗粒数的增加（p <0.05）。 CP-154,526废除了Cortagine诱导的粪便颗粒的输出（P <0.05）。 EMG的幅度在四组之间具有显着差异（p <0.01）。在用皮质素处理的大鼠中，EMG振幅明显高于对照组和CP组（P <0.05）。与皮质基组相比，CP-154,526的振幅显着降低（p <0.05）。 EPM的总行进距离在四组之间具有显着差异（p = 0.01）。 结论：我们的结果表明，外周皮质注射可以刺激大鼠的排便并诱导大鼠内脏的超敏反应，而大鼠被CRH-R1拮抗剂废除。周围皮质激素可能引起与焦虑相关的行为，而CRH-R1拮抗剂减少了焦虑行为。

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

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/Peking Union Medical College(中国)

中日友好医院/北京协和医学院（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.

China-Japan Friendship Hospital(China)

中日友好医院（中国）