並列タイトル等アンジオテンシン受容体拮抗薬は、肝硬変ラットの骨格筋萎縮に対して、分岐鎖アミノ酸製剤による保護効果を増強する。
一般注記type:Thesis
Scope: This study investigated the combined effect of the angiotensin II(AT-II) receptor blocker losartan and branched-chain amino acids (BCAAs) onskeletal muscle atrophy in rats with cirrhosis and steatohepatitis.Method and Results: Fischer 344 rats are fed a choline-deficient l-aminoacid-defined (CDAA) diet for 12 weeks and treated with oral losartan (30 mgkg−1 day−1) and/or BCAAs (Aminoleban EN, 2500 mg kg−1 day−1). Treatmentwith losartan and BCAAs attenuated hepatic inflammation and fibrosis andimproved skeletal muscle atrophy and strength in CDAA-fed rats. Both agentsreduced intramuscular myostatin and pro-inflammatory cytokine levels,resulting in inhibition of the ubiquitin–proteasome system (UPS) throughinterference with the SMAD and nuclear factor-kappa B pathways,respectively. Losartan also augmented the BCAA-mediated increase of skeletalmuscle mass by promoting insulin growth factor-I production andmitochondrial biogenesis. Moreover, losartan decreased the intramuscularexpression of transcription factor EB (TFEB), a transcriptional inducer of E3ubiquitin ligase regulated by AT-II. In vitro assays illustrated that losartanpromoted mitochondrial biogenesis and reduced TFEB expression inAT-II-stimulated rat myocytes, thereby potentiating the inhibitory effects ofBCAAs on the UPS and caspase-3 cleavage.Conclusion: These results indicate that this regimen could serve as a noveltreatment for patients with sarcopenia and liver cirrhosis.
博士（医学）・甲第861号・令和5年3月15日
This is the peer reviewed version of the following article: [Soichi, Takeda et al. Angiotensin Receptor Blockers Potentiate the Protective Effect of Branched-Chain Amino Acids on Skeletal Muscle Atrophy in Cirrhotic Rats. Molecular Nutrition & Food Research. 2021, 65(24), 2100526.], which has been published in final form at [https://doi.org/10.1002/mnfr.202100526]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.
identifier:Molecular nutrition & food research.,Vol.65 No.24 Article No.e2100526 (2021 Dec)
identifier:16134125
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4092
identifier:Molecular nutrition & food research., 65(24): e2100526
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