著者

竹下 舜也 日比 千尋 坂本 多穗 黒川 洵子

出版者

公益社団法人 日本薬理学会

雑誌

日本薬理学会年会要旨集 第94回日本薬理学会年会 (ISSN:24354953)

巻号頁・発行日

pp.3-P2-25, 2021 (Released:2021-03-21)

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Intensive care unit-acquired weakness (ICU-AW) is a sepsis-induced myopathy characterized by reductions in muscle force-generation, mass, and bioenergetics, leading to severe difficulties in breathing, swallowing, and exercise. Since males are more prone to sepsis and aromatase inhibitors worsen critical illness, we investigated the effect of 17β-estradiol (E2) on septic symptoms in skeletal muscle in an in vivo and in vitro. E2 treatment attenuated cecal ligation puncture (CLP)-induced loss of grip strength in ovariectomized (OVX) mice and preserve contractility of extensor digitorum longus muscle from OVX mice underwent CLP. E2 significantly attenuated lipopolysaccharide (LPS)-induced atrophy and induction of inflammatory cytokine mRNAs (TNFα and IL6) in mouse C2C12 myotubes. Furthermore, E2 significantly inhibited the LPS-induced increase of mtDNA, a driver of pro-inflammatory signals. Our results show that E2 attenuates inflammation through mitochondrial protection by inhibiting the increase in mtDNA, which also attenuates muscle weakness and atrophy. We anticipate that our results will lead to a more detailed mechanism analysis of attenuation of muscle weakness and atrophy by E2, as well as to elucidate gender differences in sepsis-induced ICU-AW.