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Development of preventive treatment method by creating focal intestinal perforation rat model associated with prematurity aiming at improvement of neurological prognosis

Research Project

Project/Area Number 20K22958
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0905:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionKagoshima University

Principal Investigator

SUGITA Koshiro  鹿児島大学, 鹿児島大学病院, 特任助教 (50781514)

Project Period (FY) 2020-09-11 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords限局性腸穿孔 / FIP / 新生児消化管穿孔 / 動物モデル / NEC / 母体ストレス
Outline of Research at the Start

新生児外科疾患の救命率は改善しているが、新生児壊死性腸炎(NEC)や特発性腸穿孔(FIP)などの外科治療介入を行った児の神経学的発達の予後は必ずしも思わしいものではなくまた疾患の病態生理は未だに解明されず、抜本的な予防・治療法の開発が待たれている。我々はこれまで疾患モデルラットを使ったNECの病態解明を行い、消化管ホルモンや抗真菌薬、漢方薬による新規治療法の開発研究を継続してきた。今回我々は、FIPにおける臨床経験を元に、FIPが母体へのストレスから発症するのではないかという発想を得た。本研究はFIPの疾患モデルラットの新規開発、そのモデルラットを使用した病態解明および新規予防法の開発を目的とする。

Outline of Final Research Achievements

Based on the hypothesis that the mechanism that causes diving reflex is the two stimulations of "infection" and "hypoxia" conducted in this study, an animal model was created by two-step stress stimulation, "maternal" and "postnatal" was verified.
The purpose was to reproduce the diving reflex and FIP model by performing it on pregnant rats, but no results were obtained to develop FIP. Human stress hormones are endogenous steroids that are favored in the adrenal glands, but prenatal fetal stress hormones are said to be vasopressin, which has a stronger vasoconstrictor effect. We will continue to explore the selection of reagents and stimuli for stress during pregnancy in order to reproduce the diving reflex, and we believe that further research is needed to create an FIP model.

Academic Significance and Societal Importance of the Research Achievements

FIPは超低出生体重児に発症するが、希少疾患であるため臨床情報からだけではエビデンスが得られにくい。2年間の本研究期間中に低酸素刺激とLPS刺激だけではFIPモデルを作成することはできなかった。作成を試みた結果、NECとの病態的な違いにより一層着目していく必要を認識した。FIPはNECと異なり典型的には回盲部領域に発生する、回盲部領域の血流を評価することや血流が低下する原因として胎児ストレスホルモンの関連性などを明らかにしていく着想に至り、今後の研究課題を得られたという意味では有意義であったと思われた
。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (16 results)

All 2021 2020

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (9 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] The protective effects of hepatocyte growth factor on the intestinal mucosal atrophy induced by total parenteral nutrition in a rat model2021

    • Author(s)
      Sugita Koshiro、Kaji Tatsuru、Yano Keisuke、Matsukubo Makoto、Nagano Ayaka、Matsui Mayu、Murakami Masakazu、Harumatsu Toshio、Onishi Shun、Yamada Koji、Yamada Waka、Muto Mitsuru、Kumagai Kotaro、Ido Akio、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 37 Issue: 12 Pages: 1743-1753

    • DOI

      10.1007/s00383-021-05002-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Potential predictors of the onset of focal intestinal perforation in extremely low birth weight infants based on an analysis of coagulation and fibrinolysis markers at birth: A case-control study based on ten years of experience at a single institution2021

    • Author(s)
      Sugita Koshiro、Ibara Satoshi、Harumatsu Toshio、Ishihara Chie、Naito Yoshiki、Murakami Masakazu、Machigashira Seiro、Noguchi Hiroyuki、Muto Mitsuru、Matsukubo Makoto、Ieiri Satoshi
    • Journal Title

      Journal of Pediatric Surgery

      Volume: 56 Issue: 7 Pages: 1121-1126

    • DOI

      10.1016/j.jpedsurg.2021.03.043

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The administration of hepatocyte growth factor prevents total parenteral nutrition-induced hepatocellular injury in a rat model2021

    • Author(s)
      Matsukubo Makoto、Yano Keisuke、Kaji Tatsuru、Sugita Koshiro、Onishi Shun、Harumatsu Toshio、Nagano Ayaka、Matsui Mayu、Murakami Masakazu、Yamada Koji、Yamada Waka、Muto Mitsuru、Kumagai Kotaro、Ido Akio、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 37 Issue: 3 Pages: 353-361

    • DOI

      10.1007/s00383-020-04823-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Discrepancy between the survival rate and neuropsychological development in postsurgical extremely low-birth-weight infants: a retrospective study over two decades at a single institution2021

    • Author(s)
      Muto Mitsuru、Sugita Koshiro、Ibara Satoshi、Masuya Ryuta、Matuskubo Makoto、Kawano Takafumi、Saruwatari Yumiko、Machigashira Seiro、Sakamoto Koichi、Nakame Kazuhiko、Shinyama Shin、Torikai Motofumi、Hayashida Yoshihiro、Mukai Motoi、Ikee Takamasa、Shimono Ryuichi、Noguchi Hiroyuki、Ieiri Satoshi
    • Journal Title

      Pediatric Surgery International

      Volume: 37 Issue: 3 Pages: 411-417

    • DOI

      10.1007/s00383-020-04825-7

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Successful laparoscopic extirpation of a vasoactive intestinal polypeptide‐secreting neuroblastoma originating from the right adrenal gland: A report of an infantile case2021

    • Author(s)
      Sugita Koshiro、Kaji Tatsuru、Muto Mitsuru、Nishikawa Takuro、Okamoto Yasuhiro、Imamura Mari、Ieiri Satoshi
    • Journal Title

      Asian Journal of Endoscopic Surgery

      Volume: - Issue: 3 Pages: 611-614

    • DOI

      10.1111/ases.12916

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prophylactic efficacy of enteral antifungal administration of miconazole for intestinal perforation, especially for necrotizing enterocolitis: a historical cohort study at a single institution2020

    • Author(s)
      Torikai Motofumi、Sugita Koshiro、Ibara Satoshi、Ishihara Chie、Kibe Masaya、Murakami Kenichi、Shinyama Shin、Mukai Motoi、Ikee Takamasa、Sueyoshi Kazunobu、Noguchi Hiroyuki、Ieiri Satoshi
    • Journal Title

      Surgery Today

      Volume: 51 Issue: 4 Pages: 568-574

    • DOI

      10.1007/s00595-020-02125-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] IFALDの病態解明に基づくGLP-2を用いた新規治療法の開発2020

    • Author(s)
      矢野 圭輔, 杉田 光士郎, 家入 里志
    • Journal Title

      Medical Science Digest

      Volume: 46(7) Pages: 437-440

    • Related Report
      2020 Research-status Report
  • [Presentation] 新生児壊死性腸炎から短腸症候群に陥った超低出生体重児症例の1例-2つの特殊脂肪乳剤による栄養管理の経験2021

    • Author(s)
      杉田 光士郎, 武藤 充, 指宿 卓也, 瀬戸口 誠, 有馬 順子, 町頭 成郎, 野口 啓幸
    • Organizer
      第36回日本臨床栄養代謝学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 肝細胞増殖因子(HGF)による腸粘膜上皮再生への試み 完全静脈栄養ラットモデルを用いた小腸粘膜上皮へ与える効果に関する検討2021

    • Author(s)
      杉田 光士郎, 加治 建, 矢野 圭輔, 松久保 眞, 祁答院 千寛, 松井 まゆ, 村上 雅一, 春松 敏夫, 大西 峻, 山田 耕嗣, 山田 和歌, 武藤 充, 熊谷 公太郎, 井戸 章雄, 家入 里志
    • Organizer
      第37回日本小児外科学会秋季シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] 超低出生体重児の限局性腸穿孔に関する凝固線溶系分析に基づいた潜在的な発症予測因子の検討2021

    • Author(s)
      杉田 光士郎, 茨 聡, 石原 千詠, 武藤 充, 内藤 喜樹, 山本 将功, 山本 剛士, 木部 匡哉, 大橋 宏史
    • Organizer
      第65回日本新生児成育医学会・学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 超低出生体重児における限局性腸穿孔 出生時の凝固線溶系分析により発症を予測することは可能か?2021

    • Author(s)
      杉田 光士郎, 茨 聡, 鳥飼 源史, 武藤 充, 石原 千詠, 内藤 喜樹, 村上 雅一, 町頭 成郎, 春松 敏夫, 松久 保眞, 家入 里志
    • Organizer
      第57回日本周産期・新生児医学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Potential onset predictive factors for focal intestinal perforation in extremely-low-birth-weight infants based on a coagulation and fibrinolysis system analysis at birth: Ten years’ experience at a single institution2020

    • Author(s)
      Koshiro Sugita, Satoshi Ibara, Toshio Harumatsu, Chie Ishihara, Yoshiki Naito, Masakazu Murakami, Seiro Machigashira, Hiroyuki Noguchi, Makoto Matsukubo, Mitsuru Muto, Satoshi Ieiri
    • Organizer
      The 53th Pacific Association of Pediatric Surgeons
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] The Clinical Characteristics of Focal Intestinal Perforation in ELBWIs on Enteral Prophylactic Miconazole: A Historical Cohort Study Based on a 10-Year Experience at a Single Center2020

    • Author(s)
      K Sugita, M Torikai, S Ibara, T Harumatsu, C Ishihara, Y Naito, M Murakami, M Matsukubo, M Muto, T Kawano, S Machigashira, H Noguchi, S Ieiri
    • Organizer
      The 33th 3International Symposium on Pediatric Surgical Research
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Management and Outcome of abdominal wall defects associated with gastroschisis and omphalocele: Based on over 30-Year Experience at Bicenter2020

    • Author(s)
      K Sugita, M Matsukubo, K Nakame, A Nagano, M Matsui, M Murakami, M Kawano, K Yano, S Onishi, T Harumatsu, K Yamada, W Yamada, M Muto, T kaji, H Noguchi, S Ieiri
    • Organizer
      The 33th 3International Symposium on Pediatric Surgical Research
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新生児壊死性腸炎後の短腸症候群の1例2020

    • Author(s)
      杉田光士郎、茨聡、栗本朋典、村上雅一、町頭成郎、武藤充、野口啓幸
    • Organizer
      第63回鹿児島栄養代謝研究会
    • Related Report
      2020 Research-status Report
  • [Presentation] 当院での超低出生体重児の鼠径ヘルニアに対する治療戦略及び成績-単一施設での過去10年の経験から2020

    • Author(s)
      杉田光士郎、野口啓幸、村上雅一、松久保眞、町頭成郎、家入里志
    • Organizer
      第57回日本小児外科学会
    • Related Report
      2020 Research-status Report

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Published: 2020-09-29   Modified: 2023-01-30  

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