The effect of ghrelin on intestinal mucosal atrophy during total parenteral nutrition

• Project/Area Number: 16K10434
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Kagoshima University
• Principal Investigator: YAMADA Waka 鹿児島大学, 医歯学域附属病院, 特任助教 (20457659)
• Co-Investigator(Kenkyū-buntansha): 家入 里志 鹿児島大学, 医歯学域医学系, 教授 (00363359) ; 谷本 昭英 鹿児島大学, 医歯学域医学系, 教授 (10217151) ; 川野 孝文 鹿児島大学, 医歯学総合研究科, 客員研究員 (40457651) ; 加治 建 鹿児島大学, 附属病院, 特任教授 (50315420) ; 中目 和彦 鹿児島大学, 医歯学域附属病院, 講師 (70448570) ; 向井 基 鹿児島大学, 医歯学域医学系, 准教授 (80468024) ; 山田 耕嗣 鹿児島大学, 附属病院, 医員 (80528042) ; 大西 峻 鹿児島大学, 附属病院, 医員 (10614638)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 大量小腸切除 / 短腸症候群 / 長期絶食 / 腸管萎縮 / Acyl-ghrelin / 腸管順応 / Glucagon-like peptide-2 / 新生児 / グレリン / 消化管 / 経静脈栄養

Outline of Final Research Achievements

We prepared long-term fasted parenteral nutrition model rats and reproduced atrophy of intestinal mucosa by long-term fasting. Subsequently, ghrelin was administered to this model rat, and the effect on intestinal atrophy was examined. As a result, the atrophy of the villi and crypt depth in the jejunum was alleviated, and it was judged that it had an effective action on atrophy of the small intestine mucosa. Next, in order to reproduce short bowel syndrome and examine the effect of ghrelin on intestinal adaptation after intestinal resection, an 80% short bowel model rat was prepared and administered with ghrelin. As a result, although there was a result that ghrelin administration suggested the intestinal adaptation promotion of the remaining intestinal tract, the mechanism of action, the specific optimal administration timing, and the examination of dosage amount have not been reached, and further studies are needed in the future.

Academic Significance and Societal Importance of the Research Achievements

経静脈栄養により長期間の絶食が可能となったが、QOLの低下や消化管粘膜の萎縮、経静脈栄養関連肝障害などの合併症が生じうる。これらを回避するには早期経腸栄養への移行が鍵となるが、腸管順応の機序は未だ不明である。一方、成長ホルモン分泌促進作用を有する消化管ホルモンであるグレリン（Ghrelin）は、生体内組織の修復・成長に関わる様々な生理作用を発揮するペプチドである。そこで、グレリンが腸管粘膜萎縮予防と残存腸管の順応にどのように作用するかを検討した。今回の研究で、グレリンの腸管粘膜萎縮予防や腸管順応への効果的な作用が示唆されたため、今後さらなる研究を重ね、臨床応用へと繋げていけると考えている。

Research Products

• [Journal Article] Ghrelin Stimulates Intestinal Adaptation Following Massive Small Bowel Resection (2018)
  • Author(s): Onishi S, Kaji T, Yamada W, Nakame K, Machigashira S, Yano K, Kawano M, Harumatsu T,Masuya R, Kawano T, Mukai M, Yoshioka T, Souda M, Hamada T, Tanimoto A, Ieiri S
  • Journal Title: Peptide Volume: 106 Pages: 264-267
  • DOI: 10.1016/j.peptides.2018.06.009
  • Peer Reviewed / Open Access
• [Journal Article] Long-term outcomes of surgery for choledochal cysts: a single-institution study focusing on follow-up and late complications (2018)
  • Author(s): Mukai Motoi、Kaji Tatsuru、Masuya Ryuta、Yamada Koji、Sugita Koshiro、Moriguchi Tomoe、Onishi Shun、Yamada Waka、Kawano Takafumi、Machigashira Seiro、Nakame Kazuhiko、Takamatsu Hideo、Ieiri Satoshi
  • Journal Title: Surgery Today Volume: 48 Issue: 9 Pages: 835-840
  • DOI: 10.1007/s00595-018-1660-9
  • Peer Reviewed / Open Access
• [Journal Article] The effect of intravenous lipid emulsions and mucosal adaptation following massive bowel resection (2018)
  • Author(s): Onishi Shun、Kaji Tatsuru、Machigashira Seiro、Yamada Waka、Masuya Ryuta、Nakame Kazuhiko、Kawano Masato、Yano Keisuke、Yamada Koji、Kawano Takafumi、Mukai Motoi、Yoshioka Takako、Tanimoto Akihide、Ieiri Satoshi
  • Journal Title: Journal of Pediatric Surgery Volume: 53 Issue: 12 Pages: 2444-2448
  • DOI: 10.1016/j.jpedsurg.2018.08.019
  • Peer Reviewed / Open Access
• [Journal Article] Predictors of a successful outcome for infants with short bowel syndrome: a 30-year single-institution experience (2017)
  • Author(s): Kaji Tatsuru、Nakame Kazuhiko、Machigashira Seiro、Kawano Takafumi、Masuya Ryuta、Yamada Waka、Yamada Koji、Onishi Shun、Moriguchi Tomoe、Sugita Koshiro、Mukai Motoi、Ieiri Satoshi
  • Journal Title: Surgery Today Volume: 47 Issue: 11 Pages: 1391-1396
  • DOI: 10.1007/s00595-017-1534-6
  • Peer Reviewed / Open Access
• [Journal Article] Current characteristics and management of congenital esophageal stenosis: 40 consecutive cases from a multicenter study in the Kyushu area of Japan (2017)
  • Author(s): Suzuhigashi Masaya、Kaji Tatsuru、Noguchi Hiroyuki、Muto Mitsuru、Goto Michiko、Mukai Motoi、Nakame Kazuhiko、Kawano Takafumi、Yamada Waka、Yamada Koji、Onishi Shun、Ieiri Satoshi
  • Journal Title: Pediatric Surgery International Volume: 33 Issue: 10 Pages: 1035-1040
  • DOI: 10.1007/s00383-017-4133-0
  • Peer Reviewed / Open Access
• [Journal Article] A comparison of the characteristics and precision of needle driving for right-handed pediatric surgeons between right and left driving using a model of infant laparoscopic diaphragmatic hernia repair (2017)
  • Author(s): Ikee Takamasa、Onishi Shun、Mukai Motoi、Kawano Takafumi、Sugita Koshiro、Moriguchi Tomoe、Yamada Koji、Yamada Waka、Masuya Ryuta、Machigashira Seiro、Nakame Kazuhiko、Kaji Tatsuru、Ieiri Satoshi
  • Journal Title: Pediatric Surgery International Volume: 33 Issue: 10 Pages: 1103-1108
  • DOI: 10.1007/s00383-017-4144-x
  • Peer Reviewed / Open Access
• [Journal Article] The bowel function and quality of life of Hirschsprung disease patients who have reached 18 years of age or older ? the long-term outcomes after undergoing the transabdominal soave procedure (2017)
  • Author(s): Onishi Shun、Nakame Kazuhiko、Kaji Tatsuru、Kawano Masato、Moriguchi Tomoe、Sugita Koshiro、Yano Keisuke、Nomura Mioko、Yamada Koji、Yamada Waka、Masuya Ryuta、Kawano Takafumi、Machigashira Seiro、Mukai Motoi、Ieiri Satoshi
  • Journal Title: Journal of Pediatric Surgery Volume: 52 Issue: 12 Pages: 2001-2005
  • DOI: 10.1016/j.jpedsurg.2017.08.036
  • Peer Reviewed / Open Access
• [Journal Article] The protective effect of fish oil lipid emulsions on intestinal failure-associated liver disease in a rat model of short-bowel syndrome (2017)
  • Author(s): Machigashira Seiro、Kaji Tatsuru、Onishi Shun、Yamada Waka、Yano Keisuke、Yamada Koji、Masuya Ryuta、Kawano Takafumi、Nakame Kazuhiko、Mukai Motoi、Ieiri Satoshi
  • Journal Title: Pediatric Surgery International Volume: 34 Issue: 2 Pages: 203-209
  • DOI: 10.1007/s00383-017-4190-4
  • Peer Reviewed / Open Access
• [Journal Article] Ghrelin Improves Intestinal Mucosal Atrophy During Parenteral Nutrition: An Experimental Study (2016)
  • Author(s): Yamada W, Kaji T, Onishi S, Nakame K, Yamada K, Kawano T, Mukai M, Souda M, Yoshioka T, Tanimoto A, Ieiri S
  • Journal Title: J Pediatr Surg Volume: 51(12) Issue: 12 Pages: 2039-2043
  • DOI: 10.1016/j.jpedsurg.2016.09.035
  • Peer Reviewed / Open Access
• [Presentation] Left Thoracoscopic Approach for a Bronchogenic Cyst Originating from the Lower Esophagus (2018)
  • Author(s): Yano K, Kawano T, Nonaka Y, Onishi S, Kawano M, Yamada K, Yamada W, Masuya R,Machigashira S, Nakame K, Mukai M, Kaji T, Ieiri S
  • Organizer: IPEG
  • Int'l Joint Research
• [Presentation] Strategy of Neonatal Airway Obstruction with Team Medical Care (2018)
  • Author(s): Onishi S, Nakame K, Yano K, Harumatsu T, Yamada K, Yamada W, Masuya R, Kawano T, Machigashira S, Mukai M, Kaji T, Ieiri S
  • Organizer: The Federation of Asia and Oceania Perinatal Societies
  • Int'l Joint Research
• [Presentation] 【要望演題10：トランスレーショナルリサーチ】短腸症候群の予後改善に向けたトランスレーショナルリサーチ －研究から臨床への適応拡大をめざして－Translational research to improve the prognosis for the patients with short bowel (2018)
  • Author(s): 加治 建，大西 峻，村上雅一，川野正人，矢野圭輔，山田耕嗣，山田和歌，桝屋隆太，川野孝文，町頭成郎，中目和彦，向井 基，家入里志
  • Organizer: 第55回日本小児外科学会学術集会
• [Presentation] 短腸症候群モデルラットを用いた腸管不全合併肝障害(IFALD)に対するω3系脂肪乳剤の肝障害予防効果の検討 (2018)
  • Author(s): 町頭 成郎、加治 建、矢野圭輔、川野正人、大西 俊、山田耕嗣、山田和歌、桝屋隆太、川野孝文、中目和彦、向井 基、家入里志
  • Organizer: 第55回日本外科代謝栄養学会定期学術集会
• [Presentation] 短腸症候群における残存腸管順応と肝障害に対するグレリンの治療効果 モデルラットを用いた新たな治療法の開発 (2018)
  • Author(s): 大西 峻, 加治 建, 町頭 成郎, 山田 和歌, 川野 正人, 矢野 圭輔, 山田 耕嗣, 桝屋 隆太, 川野 孝文, 中目 和彦, 向井 基, 家入 里志
  • Organizer: 第118回日本外科学会定期学術集会