Novel Therapeutic Targets for Functional Gastrointestinal Disorders

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08019
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Takashi Kondo 兵庫医科大学, 医学部, 講師 (90594870)
• Co-Investigator(Kenkyū-buntansha): 三輪 洋人 兵庫医科大学, 医学部, 教授 (80190833)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 機能性消化管疾患 / 内臓知覚過敏

Outline of Final Research Achievements

The underlying mechanism between micro-inflammation and FD remains unknown. In this study, using a maternal separation (MS)-induced FD model, we aimed to reproduce the gastroduodenal micro-inflammation and reveal the interaction of gastroduodenal micro-inflammation and gastric hypersensitivity. MS model was established by separating newborn Sprague Dawley rats for 2 h a day from postnatal day 1 to 10. At 7-8 weeks of age, electromyography was used to determine the visceromotor response to gastric distention (GD). MS-induced FD rats underwent gastric hypersensitivity with GD. Eosinophils were significantly increased in the gastroduodenal tract. Treatment with dexamethasone reversed gastric hypersensitivity in MS-induced FD rats by inhibiting eosinophil infiltration. Our results indicate that neonatal MS stress induces eosinophil-associated gastroduodenal micro-inflammation and gastric hypersensitivity at adulthood in rats. Micro-inflammation contributes to gastric hypersensitivity.

Free Research Field

神経消化器病学

Academic Significance and Societal Importance of the Research Achievements

今回の研究成果により，生直後のストレスが引き金となり，成長後に胃十二指腸粘膜内での好酸球増加を主とする微小炎症を引き起こすこと，その結果として胃十二指腸粘膜の知覚過敏に結びついている可能性が示唆された。このことは，機能性消化管疾患患者の症状発現メカニズムの病態解明に結びつき新たな治療ターゲットの発見に結びつくものと考える。