Whole transcriptome analysis of the brain in a shrew model of postoperative nausea and vomiting

Research Project

Project/Area Number	16K10951
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Anesthesiology
Research Institution	Tohoku University
Principal Investigator	Sugino Shigekazu 東北大学, 大学病院, 助教 (00423765)
Research Collaborator	KONNO Daisuke SUZUKI Jun MISAWA Kazuharu SHIBATA Tomoko KAWAI Yosuke IMAMURA Yuka NAGASAKI Masao KIDO Kanta
Project Period (FY)	2016-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000) Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	術後悪心嘔吐 / PONV / スンクス / 次世代DNAシークエンサー / トランスクリプトーム解析 / 孤束核 / 嘔吐中枢 / 外科 / ゲノム / 行動学 / 悪心嘔吐 / 脳・神経
Outline of Final Research Achievements	Postoperative nausea and vomiting (PONV) is a serious complication after emergence from general anesthesia. However, the molecular mechanisms underlying PONV have not been fully elucidated. Musk shrews are used for emetic research worldwide because standard laboratory animals, such as rats and mice, are not capable of vomiting. The aims of this study were to determine changes in gene expression in the shrew brainstem and to try to determine the causative genes for PONV. The results of a behavioral study showed that emetic episodes occurred in the PONV model shrews but not in naive shrews. Whole transcriptome sequencing showed that EGR1 gene expression levels in the gonadotropin-releasing hormone signaling pathway were significantly altered in the PONV model. We focused on EGR1 transcription factor as a candidate associated with PONV. The findings suggested that the change in EGR1 gene expression level may be involved in the molecular mechanisms underlying the development of PONV.
Academic Significance and Societal Importance of the Research Achievements	PONVは術後の合併症の中でも20-30%の高い頻度で起こる不快な合併症の1つである．PONVの臨床的危険因子は大規模研究ですでに明らかになっており，全身麻酔法の決定に影響を与えているが，PONVを完全に予防することは困難で，患者の医療に対する満足度を下げてしまうことも多い．それにもかかわらず，本邦の周術期医療では保険診療上，制吐薬の使用は選択肢があまりなく，効果の高い新規の制吐薬の開発が待望されている．本研究ではEGR1転写因子をはじめとした複数の制吐薬の標的候補を同定できた．今後は新たな制吐薬と手術後での使用を視野に入れて，さらに研究を推進したい．