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Development of the new therapy using glucagon like peptide -2 for the necrotising enterocolitis

Research Project

Project/Area Number 16K10094
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

Kazuhiko Nakame  鹿児島大学, 医歯学域附属病院, 講師 (70448570)

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)
山田 和歌  鹿児島大学, 医歯学域附属病院, 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, 附属病院, 特任教授 (50315420)
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 *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords壊死性腸炎 / 新生児 / 低出生体重児 / サイトカイン / 予防 / GLP-2 / 炎症性サイトカイン / GLP-2 / ラット / 治療
Outline of Final Research Achievements

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease, that affects premature infants. Glucagon-like peptide-2 (GLP-2) is an intestinotrophic hormone and reduces the inflammation. We suspected that GLP-2 would have protective and anti-inflammatory effects in an experimental rat model of NEC. NEC was induced in newborn rats by enteral feeding with hyperosmolar formula, asphyxial stress and enteral administration of lipopolysaccharide (LPS). Rats were randomly divided into the following four groups: dam-fed, NEC, NEC+GLP-2(low dose), and NEC+GLP-2(high dose). The NEC score and the survival rate in the NEC+GLP-2(H) group was improved compared with those in the NEC and the NEC+GLP-2(L) groups. High dose GLP-2 administration improved the incidence and survival rate for NEC. It also decreased ileal mucosal inflammatory cytokine production. These results support a potential therapeutic role for GLP-2 in the treatment of NEC.

Academic Significance and Societal Importance of the Research Achievements

壊死性腸炎は新生児、特に低出生体重児に発症する腸管の壊死を伴う腸管不全であり、高率な死亡率(約40%)を有する疾患である。近年、早産児、低出生体重児の出生数が増加しており、それに伴い生存率を高めるだけでなく、intact survival(後遺症なき生存)が目指されている。一方、グルカゴンライクペプチドー2(GLP-2)は腸管に対する成長因子、抗炎症作用を有するペプチドであり、短腸症候群・炎症性腸疾患への臨床応用が期待されている。現在、日本でも短腸症候群に対して臨床試験が進行している。当研究は壊死性腸炎ラットモデルを用いてGLP-2の治療効果を証明した。壊死性腸炎への臨床応用が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (25 results)

All 2018 2017 2016

All Journal Article (16 results) (of which Peer Reviewed: 16 results,  Open Access: 16 results) Presentation (9 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Three Cases of Pyriform Sinus Fistula Presenting With Respiratory Distress in the Neonatal Period and a Review of the Literature in Japan2018

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

      Journal of the Japanese Society of Pediatric Surgeons

      Volume: 54 Issue: 5 Pages: 1117-1123

    • DOI

      10.11164/jjsps.54.5_1117

    • NAID

      130007437292

    • ISSN
      0288-609X, 2187-4247
    • Year and Date
      2018-08-20
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A rare case of ectopic pancreas presenting with persistent umbilical discharge2018

    • Author(s)
      Nakame K, Hamada R, Suzuhigashi M, Nanashima A, Ieiri S
    • Journal Title

      Pediatrics International

      Volume: 60 Issue: 9 Pages: 891-892

    • DOI

      10.1111/ped.13637

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term outcomes of surgery for choledochal cysts: a single-institution study focusing on follow-up and late complications2018

    • 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

    • Related Report
      2018 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 Annual Research 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 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mediastinal mature teratoma causing cardiac tamponade—A pediatric case report2018

    • Author(s)
      中目 和彦、岡本 康裕、加治 建、河野 嘉文、家入 里志、山田 和歌、川野 孝文、町頭 成郎、上野 健太郎、西川 拓朗、田邊 貴幸、向井 基、義岡 孝子
    • Journal Title

      The Japanese Journal of Pediatric Hematology / Oncology

      Volume: 55 Issue: 5 Pages: 427-431

    • DOI

      10.11412/jspho.55.427

    • NAID

      130007580407

    • ISSN
      2187-011X, 2189-5384
    • Related Report
      2018 Annual Research 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] Identification of a novel variant of the RET proto-oncogene in a novel family with Hirschsprung’s disease2017

    • Author(s)
      Kawano Takafumi、Hosomichi Kazuyoshi、Inoue Ituro、Shimono Ryuichi、Onishi Shun、Nakame Kazuhiko、Kaji Tatsuru、Matsufuji Hiroshi、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 33 Issue: 10 Pages: 1041-1046

    • DOI

      10.1007/s00383-017-4134-z

    • Related Report
      2017 Research-status Report
    • 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 Japan2017

    • 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

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The novel preventive effect of Daikenchuto (TJ-100), a Japanese herbal drug, against neonatal necrotizing enterocolitis in rats2017

    • Author(s)
      Shinyama Shin、Kaji Tatsuru、Mukai Motoi、Nakame Kazuhiko、Matsufuji Hiroshi、Takamatsu Hideo、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 33 Issue: 10 Pages: 1109-1114

    • DOI

      10.1007/s00383-017-4145-9

    • 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
  • [Journal Article] Ghrelin Improves Intestinal Mucosal Atrophy During Parenteral Nutrition: An Experimental Study2016

    • 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

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Long-term outcome of bowel function for 110 consecutive cases of Hirschsprung's disease: Comparison of the abdominal approach with transanal approach over 30 years in a single institution : Is the transanal approach truly beneficial for bowel function?2016

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

      J Pediatr Surg

      Volume: 51(12) Issue: 12 Pages: 2010-2014

    • DOI

      10.1016/j.jpedsurg.2016.09.029

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changing Profile of Safe Techniques for Insertion a Central Venous Catheter in Pediatric Patients - Improvement in Outcomes with the Experience of 500 Insertions in a Single Institution2016

    • Author(s)
      Kaji T, Kawano T, Yamada W, Yamada K, Onishi S, Nakame K, Mukai M, Ieiri S, Takamatsu H
    • Journal Title

      J Pediatr Surg

      Volume: 51 Issue: 12 Pages: 2044-2047

    • DOI

      10.1016/j.jpedsurg.2016.09.037

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The administration of ghrelin improved hepatocellular injury following parenteral feeding in a rat model of short bowel syndrome.2016

    • Author(s)
      Onishi S, Kaji T, Yamada Y, Moriguchi T, Sugita K, Yamada K, Kawano T, Nakame K, Mukai M, Yamada S, Yoshioka T, Tanimoto A, Ieiri S
    • Journal Title

      Pediatr Surg Int

      Volume: 32(12) Issue: 12 Pages: 1165-1171

    • DOI

      10.1007/s00383-016-3975-1

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The optimum timing and surgical strategy for congenital cystic lung disease based2018

    • Author(s)
      Nakame K, Murakami M, Yano K, Baba T, Harumatsu T, Onishi S, Yamada K, Yamada W,Masuya R,Kawano T, Machigashira S, Mukai M, Kaji T, Ieiri S
    • Organizer
      20th Congress, The Federation of Asia and Oceania Perinatal Societies
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 40例の経験からみた先天性嚢胞性肺疾患の外科治療の検討―胸腔鏡手術時代の出生前診断例に対す2018

    • Author(s)
      中目和彦, 矢野圭輔, 大西 峻, 山田耕嗣, 山田和歌, 桝屋隆太, 川野孝文, 町頭成郎, 向井 基,加治 建, 家入里志
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 40例の経験からみた先天性嚢胞性肺疾患の外科治療の検討―出生前診断例に対する治療戦略―2018

    • Author(s)
      中目和彦, 川野正人, 矢野圭輔, 村上雅一, 馬場徳朗, 大西 峻, 春松敏夫, 山田耕嗣, 山田和歌,桝屋隆太, 川野孝文, 町頭成郎, 向井 基, 加治 建, 家入里志
    • Organizer
      第55回日本小児外科学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 新生児上気道狭窄に対する関連診療科との連携による治療戦略2018

    • Author(s)
      中目和彦, 矢野圭輔, 川野正人, 大西 峻, 山田耕嗣, 山田和歌, 桝屋隆太, 町頭成郎, 川野孝文,向井 基, 加治 建, 家入里志
    • Organizer
      第54回日本周産期・新生児医学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 気道外科専門外来開始後の初期導入効果に関する検討―地方小児外科拠点病院における気道外科疾患に対する取り組みー2018

    • Author(s)
      中目和彦, 連 利博, 村上雅一, 矢野圭輔, 馬場徳朗, 春松敏夫, 大西 峻, 山田耕嗣,山田和歌, 桝屋隆太, 川野孝文, 町頭成郎, 向井 基 ,加治 建, 家入里志
    • Organizer
      第29回日本小児呼吸器外科研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Nuss法による胸骨挙上術の治療成績と合併症の検討2018

    • Author(s)
      中目和彦, 村上雅一, 矢野圭輔, 大西 峻, 春松敏夫, 馬場徳朗, 山田耕嗣, 山田和歌,桝屋隆太, 町頭成郎, 向井 基, 加治 建, 家入里志
    • Organizer
      第18回Nuss法漏斗胸手術手技研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Vascular anomalyに対する治療戦略-40例 の治療経験からみた外科治療の再評価-.2017

    • Author(s)
      32.中目和彦、杉田光士郎, 森口智江, 大西 峻, 山田耕嗣, 山田和歌,桝屋隆太, 川野孝文, 町頭成郎,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
  • [Presentation] The operative results and the outcomes of treatment for abdominal wall defects- A 30-year single institution experience.2016

    • Author(s)
      Nakame K
    • Organizer
      19th Congress of the Federation of Asia and Oceania Perinatal Societies (FAOPS 2016) held
    • Place of Presentation
      Taipei(Taiwan)
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 当科における胆道閉鎖術後自己肝生存率に対する予後因子の検討2016

    • Author(s)
      中目和彦
    • Organizer
      第53回日本小児外科学会学術集会(JSPS2016)
    • Place of Presentation
      ヒルトン福岡シーホーク(福岡県・福岡市)
    • Year and Date
      2016-05-24
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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