The effects of additional antenatal betamethasone administration on postnatal ductus arteriosus closure

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17370
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Yokohama City University
• Principal Investigator: KEMMOTSU Takahiro 横浜市立大学, 医学研究科, 客員研究員 (20784713)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 動脈管 / 酸素 / bFGF / 活性酸素

Outline of Final Research Achievements

We aimed to investigate the effects of additional antenatal betamethasone administration on postnatal ductus arteriosus closure. We found that partial oxygen pressure affected remodeling of the ductus arteriosus, which may influence betamethasone-induced ductus arteriosus closure. We, therefore, focused on the effect of elevation in oxygen tension on ductus remodeling in the present study. We cultured rat DASMCs and aortic smooth muscle cells in hypoxic conditions mimicking a fetal environment (3% oxygen consentration) and then exposed them to 21% oxygen concentration. The elevation in oxygen tension increased basic fibroblast growth factor (bFGF) secretion in ductus arteriosus smooth muscle cells (DASMCs). bFGF promoted DASMC migration, resulting in forming intimal thickening which is important for anatomical closure of the ductus arteriosus.

Free Research Field

未熟児・新生児医療

Academic Significance and Societal Importance of the Research Achievements

本研究により、動脈管平滑筋細胞において出生後の酸素分圧上昇による活性酸素種活性上昇が生じ、それがbFGF産生を誘導することで血管内腔への遊走が促進されて内膜肥厚を形成し、そして器質的閉鎖を促進するという可能性が示唆された。現在未熟児動脈管開存症に対する内科的治療手段はプロスタグランジン合成阻害剤のみであり、治療不応の場合はより侵襲の高度な外科的治療に踏み切るしか方法はないが、本研究は酸素分圧の調整が未熟児動脈管開存症治療の一助になる可能性を示していると考えられ、新生児医療の更なる発展に寄与する結果を得られたと考えている。