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A treatment strategy for gastrointestinal development of premature infants: Administration of micelles derived from pulmonary surfactants and vernix caseosa in a pregnant animal model

Research Project

Project/Area Number 20K09595
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56040:Obstetrics and gynecology-related
Research InstitutionNiigata University

Principal Investigator

Nishijima Koji  新潟大学, 医歯学総合病院, 教授 (80334837)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肺サーファクタント / 胎脂 / ミセル / 早産児 / 壊死性腸炎 / 多光子イオン化飛行時間型質量分析法 / 早産 / リポソーム
Outline of Research at the Start

妊娠後期には、羊水に急激に濁りが生じる(Hook GE et al.1978)。申請者は、この羊水の濁りは、肺サーファクタントが胎脂を取り囲んで“分子集合体ミセル”を形成し、羊水中に分散するための現象である事を明らかにした。一方、乳汁中の主要なエネルギー源である長鎖脂肪酸は、腸管内で胆汁酸と反応し、“ミセル構造”をとることで消化管から吸収される。本研究は、胎児が嚥下する羊水と新生児が摂取する母乳の両者に、分子集合体ミセルが存在するという共通点に着目し、早産児の初期管理に有用な経腸栄養剤の開発を目的とする。

Outline of Final Research Achievements

We performed ultrastructural analysis of“micelles derived from surfactant TA”and“pulmonary surfactant micelles present in rabbit amniotic fluid”to investigate the pharmacokinetics of pulmonary surfactant and vernix caseosa in amniotic fluid. Cryo-transmission electron microscopy revealed the micelle structure formed by the pulmonary surfactant with the hydrophilic end facing outward and the hydrophilic end facing inward. We then examined the micelle molecules in 55 human amniotic fluid samples from 16 to 40 weeks gestation using negative staining method. The detection rate of micelles increased with advancing gestational week, suggesting that micelle molecules in human amniotic fluid could be an indicator of fetal lung maturity. Although further studies are needed, our findings elucidate the physiological interactions among pulmonary, dermal-epidermal, and gastrointestinal developmental processes, and develop early enteral nutrition for preterm infants from a new perspective.

Academic Significance and Societal Importance of the Research Achievements

妊娠後期の羊水構成成分の変化と消化管成熟との関連に着目した研究は、国内外を通じて存在しない。報告者の作成したサーファクテンミセル溶液(特許第4378531号)は、ウサギ胎仔小腸の成長と保護に関与し、ラット新生仔の壊死性腸炎発症を抑制した。今日の未熟児医療における問題点の一つは消化管の未熟性に起因する壊死性腸炎の発症であり、少子高齢化社会においては、早産児を“後遺症なく生存”させることの意義はきわめて大きい。本研究を進める事で、新たな視点に立った早産児用初期経腸栄養剤の開発が期待される。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (6 results)

All 2023 2022 2021

All Journal Article (3 results) (of which Peer Reviewed: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results)

  • [Journal Article] Obstetrical outcomes of pregnant women 50 years and older compared to those aged 45-49 years: A systematic review and meta-analysis.2023

    • Author(s)
      Sugai S, Sekizuka T, Haino K, Nonaka T, Sekine M, Yoshihara K, Nishijima K.
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: - Issue: 7 Pages: 1689-1699

    • DOI

      10.1111/jog.15662

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 巻頭言 臨床と研究の狭間で思うこと2022

    • Author(s)
      西島浩二
    • Journal Title

      新潟市医師会会報

      Volume: 611号 Pages: 1-1

    • Related Report
      2021 Research-status Report
  • [Journal Article] 早産児の消化管成熟に向けた治療戦略:肺サーファクタントと胎脂を用いた動物実験2021

    • Author(s)
      西島浩二
    • Journal Title

      日本産科婦人科学会雑誌

      Volume: 73

    • Related Report
      2020 Research-status Report
  • [Presentation] A treatment strategy for the gastrointestinal development of premature infants by administration of micelles derived from pulmonary surfactants and the vernix caseosa2022

    • Author(s)
      Nishijima K
    • Organizer
      The 74th Annual Congress of the Japan Society of Obstetrics and Gynecology Joint Conference JSOG-DGGG
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A treatment strategy for the gastrointestinal development of premature infants by administration of micelles derived from pulmonary surfactants and the vernix caseosa2022

    • Author(s)
      西島浩二
    • Organizer
      第74回日本産科婦人科学会学術講演会 Joint Conference JSOG-DGGG
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 早産児の消化管成熟に向けた治療戦略:肺サーファクタントと胎脂を用いた動物実験2021

    • Author(s)
      西島浩二
    • Organizer
      第73回日本産科婦人科学会学術講演会 シンポジウム2
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-04-28   Modified: 2024-01-30  

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