investigation for management of ductus arteriosus by cytokines

• Project/Area Number: 16K10099
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Yokohama City University
• Principal Investigator: Iwasaki Shiho 横浜市立大学, 医学部, 客員准教授 (10347338)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 動脈管 / 内膜肥厚 / 炎症 / サイトカイン / 新生児 / 早産児 / ステロイド

Outline of Final Research Achievements

We aimed to explore a new treatment strategy for prostaglandin inhibitor-resistant patent ductus arteriosus in preterm infants. Glucocorticoid is a major anti-inflammatory drug, and some observational studies have demonstrated that the prevalence of patent ductus arteriosus is lower in human preterm infants who received antenatal betamethasone. In the present study, we demonstrated that betamethasone promoted migration of smooth muscle cells isolated from rat preterm ductus arteriosus via Art3 and antenatal administration of betamethasone enhanced intimal thickening formation in preterm rat ductus arteriosus. These data suggest the beneficial role of antenatal betamethasone in the closure of preterm ductus arteriosus.

Academic Significance and Societal Importance of the Research Achievements

本研究により、分娩前母体へのベタメタゾン投与が胎仔動脈管の内膜肥厚形成を促進することが示唆された。これらは糖質コルチコイドによる動脈管リモデリングの機序をはじめて示したものである。これまで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かった。本研究は未熟児動脈管開存症の治療に新たな選択肢を示す足掛かりとなる考えられ、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。

Research Products

• [Journal Article] Antenatal Administration of Betamethasone Contributes to Intimal Thickening of the Rat Ductus Arteriosus (2019)
  • Author(s): Kemmotsu T., Yokoyama U., Saito J., Ito S., Uozumi A., Nishimaki S., Iwasaki S., Seki K., Ito S., Ishikawa Y
  • Journal Title: Circulation Journal Volume: 83 Issue: 3 Pages: 654-661
  • DOI: 10.1253/circj.CJ-18-1033
  • NAID: 130007604194
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2019-02-25
  • Peer Reviewed / Open Access
• [Presentation] ラット母体への分娩前ベタメタゾン投与が動脈管内膜肥厚へ与える作用の検討 (2018)
  • Author(s): 釼持孝博, 横山詩子, 齋藤純一, 魚住梓, 岩崎志穂, 西巻滋, 関和男, 石川義弘
  • Organizer: 第63回日本新生児成育医学会学術集会
• [Presentation] Antenatal Administration of Betamethasone Promotes Closure of the Preterm Ductus Arteriosus via Intimal Thickening Formation (2018)
  • Author(s): Kemmotsu T, Yokoyama U, Azuma S, Saito J, Ito S, Uozumi A, Iwasaki S, Nishimaki S, Ito S, Ishikawa Y.
  • Organizer: Nara Kasugano International Forum
• [Presentation] Antenatal Administration of Betamethasone Contributes to Intimal thickening of the Ductus Arteriosus (2017)
  • Author(s): Kemmothu T, Yokoyama U, Iwasaki S
  • Organizer: The 8th TAKAO International symposium
• [Presentation] 母体ラットへのベタメタゾン投与が動脈管閉鎖に与える作用の検討 (2017)
  • Author(s): 釼持孝博、横山詩子、岩崎志穂
  • Organizer: 第５３回日本新生児成育医学会学術集会