Analysis of the influence of intrauterine inflammation to adrenal function in preterm fetal infants

Research Project

Project/Area Number	17K10170
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Embryonic/Neonatal medicine
Research Institution	Tohoku University
Principal Investigator	Kitanishi Ryuta 東北大学, 医学系研究科, 非常勤講師 (20436116)
Co-Investigator(Kenkyū-buntansha)	齋藤昌利東北大学, 医学系研究科, 教授 (00451584) 埴田卓志東北大学, 大学病院, 講師 (30400360) 松田直東北大学, 医学系研究科, 非常勤講師 (50361100) 渡邊真平東北大学, 大学病院, 助教 (70509413)
Project Period (FY)	2017-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords	副腎 / 胎児 / ヒツジ / 子宮内炎症 / 超低出生体重児 / 副腎不全 / コルチゾール / 早産児 / 副腎皮質 / CRH / 胎仔 / 人工胎盤
Outline of Final Research Achievements	The study was performed to analyze the influence of intrauterine inflammation to adrenocortical ability using chronically instrumented premature fetal sheep. The fetuses were divided into two groups; control (n=9) and inflammation groups (n=11). We carried out CRH loading test. There was no difference between the two groups in the change of ACTH concentration (p=0.209) over time, but a significant difference in the change of cortisol (p=0.016). We are currently analyzing changes in the gene expression level of steroid synthase in the adrenal gland to elucidate the mechanism. However, placental control over cortisol production is added to the results of this study. Therefore, we plan to analyze changes in the gene expression level of 11b-hydroxysteroid dehydrogenase in the placenta, which converts cortisol to inactive cortisone, and changes in plasma cortisone levels.
Academic Significance and Societal Importance of the Research Achievements	今日の新生児医療において，極低出生体重児に発症する相対的副腎不全は脳虚血の遷延による深刻な脳白質損傷を誘導し，脳性麻痺や発達障害の原因となっている．その予防法の開発は周産期新生児医療の大きな課題である．本研究では胎児副腎機能の発達と出生への適応過程を明らかにするため，ヒツジ胎仔を用いた子宮内炎症モデルを応用して，出生前の炎症性ストレスがコルチゾル分泌能に与える影響を検証した．今後の研究により，出生前の子宮内環境に応じた出生後のグルココルチコイド補充療法を提案し，極低出生体重児の合併症を減少させ，その長期予後を改善できる可能性がある．