Development of a combination treatment of gastrointestinal hormones that enables the acquisition of intestinal adaptation for short bowel syndrome

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18061
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Kagoshima University
• Principal Investigator: YAMADA Waka 鹿児島大学, 医歯学域鹿児島大学病院, 特任助教 (20457659)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 長期絶食 / 腸管粘膜萎縮 / Acyl-ghrelin / Glucagon-like / peptide-2 / 腸管順応 / 経静脈栄養

Outline of Final Research Achievements

We investigated the effects of the gastrointestinal hormones ghrelin and glucagon-like peptide-2 (GLP-2) on gastrointestinal mucosal atrophy and intestinal adaptation. A combination of these hormones for long-term fasting and intravenous feeding management rats resulted in less intestinal mucosal atrophy at the time of early administration of ghrelin and late administration of GLP-2.
In addition, ghrelin and GLP-2 were co-administered for residual intestinal adaptation in a 90% short bowel rat model. Although the results show that the adaptation effect is not recognized from each single administration, further research is being carried out by examining the administration timing and dosage.

Free Research Field

小児外科

Academic Significance and Societal Importance of the Research Achievements

壊死性腸炎や多発小腸閉鎖などにより大量腸管切除を余儀なくされた小児短腸症候群らは、救命後も長期絶食、完全静脈栄養による管理を余儀なくされ、高度な栄養吸収障害と経静脈栄養関連合併症のため常に生命が脅かされる。経静脈栄養からの離脱には、腸管粘膜萎縮予防と残存腸管の腸管順応をいかに早く、効果的に行うかが鍵となる。本研究で、グレリンと現在臨床応用されている陰窩細胞増殖促進能を有するGLP-2を長期絶食、完全静脈栄養ラットモデルに投与し、それぞれ単独投与時より、腸管粘膜萎縮に相乗効果を認めた。現在はより臨床に近い短腸ラットにおける腸管順応に着手し、臨床応用につながる治療法開発を目指している。