Identification of miRNA in Dexmedetomidine-Induced Cardioprotection

Research Project

Project/Area Number	17K16745
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Anesthesiology
Research Institution	Sapporo Medical University
Principal Investigator	Yoshikawa Yusuke 札幌医科大学, 医学部, 助教 (40721759)
Project Period (FY)	2017-04-01 – 2019-03-31
Project Status	Completed (Fiscal Year 2018)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords	デクスメデトミジン / 虚血再灌流障害 / 心保護 / miRNA
Outline of Final Research Achievements	We studied differentially expressed mRNAs and miRNAs after DEX administration in rat hearts by comprehensive analysis. Additionally, bioinformatics analysis was applied to explore candidate genes and pathways that might play important roles in DEX-induced cardioprotection. The results of microarray analysis showed that 165 mRNAs and 6 miRNAs were differentially expressed after DEX administration. Through bioinformatics analysis using differentially expressed mRNAs, gene ontology (GO) terms including MAP kinase tyrosine/serine/threonine phosphatase activity and pathways including the p53 pathway were significantly enriched in the down-regulated mRNAs. On the other hand, no significant pathway was found in the target mRNAs of deregulated miRNAs. The results indicated some possible key genes and pathways that seem to be of significance in DEX-induced cardioprotection, although miRNAs seem to be unlikely to contribute to cardioprotection induced by DEX.
Academic Significance and Societal Importance of the Research Achievements	虚血性心疾患は現代社会において，成人死亡原因の多くを占める疾患であり，その制御戦略の確立が重要であることに疑いの余地はない．デクスメデトミジン (DEX) は日常臨床では手術麻酔時の鎮静薬や，集中治療室での鎮静薬として，日常的に広く使用されている薬剤である．したがって，DEXの心保護作用について解明することは，急性期医療において虚血性心疾患の予後を改善することにつながるため，重要である．本研究により，新規の新たなDEXの心保護における機序が推定された．今後更なる研究を行うことにより，虚血性心疾患の予後を改善するきっかけとなる可能性がある．