Elucidation of molecular mechanism of anti-inflammatory effects of intravenous anesthetic agents

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K18280
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55050:Anesthesiology-related
• Research Institution: Juntendo University
• Principal Investigator: Kochiyama Tsukasa 順天堂大学, 医学部, 助教 (30821722)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: プロポフォール / 静脈麻酔薬 / 抗炎症効果 / マクロファージ

Outline of Final Research Achievements

THP-1 was PMA-stimulated to (1) differentiate into macrophages, and (2) M1 differentiation was performed using these macrophages. Propofol was added at the time of M1 differentiation and the cells were cultured. The mRNA expression of GABAa receptor subtypes in cells (1) to (3) was analyzed by RT-PCR. The effects and influences of propofol on GABAa receptor subtypes during ① macrophage differentiation, ② M1 differentiation, and ③ M1 differentiation were examined by gene expression changes.
mRNA of GABAa receptor subtypes α1, α4, β1, β2, γ1, and γ2 were significantly increased. mRNA expression of α1, α4, β1, β2, and γ2 was significantly suppressed. mRNA expression of α1, α4, and β2 tended to increase.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

THP-1においてマクロファージ分化、M1分化によってGABAa受容体のサブタイプの遺伝子発現は有意に増減した。特に、炎症抑制効果に関与しているα1,α4の発現増加はプロポフォールの持つ炎症性サイトカイン抑制効果に繋がる可能性が示唆された。静脈麻酔薬の抗炎症効果の作用機序の一つとしてGABAa受容体のサブタイプが関わっていることを明らかにしたことで過剰炎症に対する治療につながる可能性がある。