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The onset mechanism elucidation using the ghrelin and development of the innovative new preventive treatment for the necrotizing enterocolitis.

Research Project

Project/Area Number 17K10183
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionKagoshima University

Principal Investigator

MACHIGASHIRA Seiro  鹿児島大学, 医歯学総合研究科, 客員研究員 (80404523)

Co-Investigator(Kenkyū-buntansha) 家入 里志  鹿児島大学, 医歯学域医学系, 教授 (00363359)
大西 峻  鹿児島大学, 医歯学総合研究科, 客員研究員 (10614638)
山田 和歌  鹿児島大学, 医歯学域鹿児島大学病院, 特任助教 (20457659)
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, 鹿児島大学病院, 特任教授 (50315420)
武藤 充  鹿児島大学, 医歯学域鹿児島大学病院, 講師 (70404522)
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, 医歯学総合研究科, 客員研究員 (80468024)
桝屋 隆太  鹿児島大学, 医学部・歯学部附属病院, その他 (90448572)
矢野 圭輔  鹿児島大学, 鹿児島大学病院, 特任助教 (30757919)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords新生児 / 壊死性腸炎 / グレリン / 低出生体重児
Outline of Final Research Achievements

Necrotizing enteritis(NEC), which is a neonatal surgical disease with a high mortality rate. Ghrelin has been reported to prevent mucosal damage in the intestinal tract and suppress inflammation. we investigated a new preventive method. We compared the following 3 mice groups; Control group: breastfeeding group, NEC group: we let NEC develop in hypoxia stimulation and LPS, Ghrelin group: ghrelin was administered to necrotic enteritis model mice.
The Ghrelin group showed less atrophy of the villi in the ileal histology than the NEC group, and the dissociation between the submucosal layer and the proper muscle layer tended to improve. The NEC scores of ileal tissues and the expression of inflammatory cytokines (TNF-α, IL-6) tended to be low, but no significant difference was shown. By further investigation high-dose ghrelin administration, it is expected that the preventive effect against necrotic enteritis will be proved.

Academic Significance and Societal Importance of the Research Achievements

壊死性腸炎は新生児外科領域で未だに高い死亡率を有する疾患であるが、現時点では明確な予防的治療法はなく発症後の外科的治療が主である。壊死性腸炎に対する予防法を確立出来れば、少子化が進む現在において後遺症なき生命予後を向上でき、また医療費削減等の社会的貢献度は非常に大きい。グレリンは成長ホルモン代謝やエネルギー代謝調整等に関わる内因性リガンドとして知られており、腸管においては炎症の誘導抑制や粘膜損傷の予防と治癒促進が報告されている。グレリンはNECに対しても予防、治療効果が期待でき、新たな治療法確立の可能性を有している。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (19 results)

All 2019 2018 2017

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Morphometrical analyses on narrowing of portal veins and thickening of hepatic arteries in the liver of biliary atresia2019

    • Author(s)
      Masuya R, Muraji T, Ohtani H, Mukai M, Onishi S, Harumatsu T, Yamada K, Yamada W, Kawano T, Machigashira S, Nakame K, Kaji T, Ieiri S
    • Journal Title

      Pediatric Surgery International

      Volume: 35 Issue: 5 Pages: 529-537

    • DOI

      10.1007/s00383-019-04459-4

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The long-term health-related quality of life of choledochal cyst patients who reach 18 years of age or older -Complications would affect mental health-2019

    • Author(s)
      Baba T, Mukai M, Masuya R, Kawano M, Yano K, Onishi S, Yamada K, Yamada W, Kawano T, Machigashira S, Nakame K, Kaji T, Ieiri S
    • Journal Title

      Pediatric Surgery International

      Volume: 35 Issue: 8 Pages: 539-546

    • DOI

      10.1007/s00383-019-04498-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The change over time in the postoperative bowel function in male anorectal malformation patients who underwent sacroperineal anorectoplasty and sacroabdominoperineal anorectoplasty.2019

    • Author(s)
      Harumatsu T, Murakami M, Yano K, Onishi S, Yamada K, Yamada W, Masuya R, Kawano T, Machigashira S, Nakame K, Mukai M, Kaji T, Ieiri S.
    • Journal Title

      Pediatric Surgery International

      Volume: 35 Issue: 10 Pages: 1109-1114

    • DOI

      10.1007/s00383-019-04540-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Impact and characteristics of two- and three-dimensional forceps manipulation using laparoscopic hepaticojejunostomy mimicking a disease-specific simulator: A comparison of pediatric surgeons with gastrointestinal surgeons2019

    • Author(s)
      Yamada K, Murakami M, Yano K, Baba T, Harumatsu T, Onishi S, Yamada W, Masuya R, Machigashira S, Nakame K, Mukai M, Kaji T, Ieiri S
    • Journal Title

      Pediatric Surgery International

      Volume: 35 Issue: 10 Pages: 1051-1057

    • DOI

      10.1007/s00383-019-04538-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel effect of glucagon-like peptide-2 for hepatocellular injury in a parenterally fed rat model of short bowel syndrome.2019

    • Author(s)
      Yano K, Kaji T, Onishi S, Machigashira S, Nagai T, Harumatsu T, Yamada K, Yamada W, Muto M, Nakame K, Mukai M, Ieiri S.
    • Journal Title

      Pediatric Surgery International

      Volume: 35 Issue: 12 Pages: 1345-1351

    • DOI

      10.1007/s00383-019-04560-8

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Ghrelin Stimulates Intestinal Adaptation Following Massive Small Bowel Resection2018

    • 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

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The effect of intravenous lipid emulsions and mucosal adaptation following massive bowel resection2018

    • 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

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two Cases of Hypertrophic Pyloric Stenosis in Patients Presenting With Prenatal Polyhydramnios2018

    • Author(s)
      町頭 成郎、家入 里志、向井 基、大西 峻、山田 耕嗣、山田 和歌、桝屋 隆太、川野 孝文、中目 和彦、加治 建
    • Journal Title

      Journal of the Japanese Society of Pediatric Surgeons

      Volume: 54 Issue: 2 Pages: 264-267

    • DOI

      10.11164/jjsps.54.2_264

    • NAID

      130006712304

    • ISSN
      0288-609X, 2187-4247
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] The protective effect of fish oil lipid emulsions on intestinal failure-associated liver disease in a rat model of short-bowel syndrome2017

    • 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

    • Related Report
      2018 Research-status Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Predictors of a successful outcome for infants with short bowel syndrome: a 30-year single-institution experience2017

    • 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

    • Related Report
      2017 Research-status Report
    • 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 repair2017

    • 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

    • Related Report
      2017 Research-status Report
    • 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 procedure2017

    • 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

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The efficiency and mechanism of ω3 fatty acid on improving intestinal failure-associated liver disease in a rat model of short bowel syndrome2019

    • Author(s)
      Machigashira S, Kaji T, Onishi S, Murakami M, Yano K, Baba T, Harumatsu T, Yamada K, Yamada W, Masuya R, Kawano T, Nakame K, Mukai M, Ieiri S
    • Organizer
      The 52nd Annual Meeting of the Pacific Association of Pediatric Surgeons
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ω3系脂肪乳剤の腸管不全合併肝障害に対する肝予防効果2019

    • Author(s)
      町頭 成郎、加治 建、大西 峻、村上雅一、矢野圭輔、馬場徳朗、春松敏夫、山田耕嗣、山田和歌、 桝屋隆太、中目和彦、向井基、家入里志
    • Organizer
      第34回日本静脈経腸栄養学会定期学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 短腸ラットモデルにおける腸管不全合併肝障害(IFALD)に対するω3系脂肪乳剤の予防効果の検討2019

    • Author(s)
      町頭 成郎、加治 建、大西峻、村上雅一、矢野圭輔、馬場徳朗、春松敏夫、山田耕嗣、山田和歌、桝屋隆太、中目和彦、向井 基、家入里志
    • Organizer
      第56回日本小児外科学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 短腸ラットモデルを用いた腸管不全合併肝障害(IFALD)に対する魚油由来脂肪乳剤の肝保護効果の検討2018

    • Author(s)
      町頭 成郎、加治 建、大西 俊、川野正人、矢野圭輔、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118回日本外科学会定期学術集会
    • Related Report
      2018 Research-status Report
  • [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
    • Related Report
      2018 Research-status Report
  • [Presentation] Does the fish oil lipid emulsion affect intestinal mucosal adaptation after massive small bowel resection in rats?2017

    • Author(s)
      1.Machigashira S、 Kaji T、Onishi S、Masuya R、Nakame K、Ieiri S
    • Organizer
      The 30th International Symposium on Pediatric Surgical Research and Update on New born
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 腹腔鏡下虫垂切除術におけるReduced Port Surgeryの導入と安全性の検証2017

    • Author(s)
      2.町頭成郎、森口智江、杉田光士郎、山田耕嗣、川野孝文、中目和彦、向井 基、加治 建、家入里志
    • Organizer
      第54回日本小児外科学会学術集会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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