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

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09595
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Niigata 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
• 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

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.

Free Research Field

周産期医学

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。