Alternative Titleリファキシミンは腸-肝臓-筋肉軸の調節により肝硬変ラットの骨格筋萎縮に対するL-カルニチンを介した予防効果を増強する
Note (General)type:Thesis
The gut‑liver‑muscle axis is associated with thedevelopment of sarcopenia in liver cirrhosis. The presentstudy aimed to illustrate the combined effects of rifaximinand L‑carnitine on skeletal muscle atrophy in cirrhotic ratswith steatohepatitis. For this purpose, a total of 344 Fischerrats were fed a choline‑deficient L‑amino acid‑defined(CD AA) diet with the daily oral administration of rifaximin(100 mg/kg) and/or L‑carnitine (200 mg/kg), and measurementsof psoas muscle mass index and forelimb grip strengthwere performed. After feeding for 12 weeks, blood samples,and liver, ileum and gastrocnemius muscle tissues wereharvested. The effects of L‑carnitine on rat myocytes wereassessed using in vitro assays. Treatment with rifaximinattenuated hyperammonemia and liver fibrosis in theCD AA‑fed rats. Moreover, it improved intestinal permeabilitywith the restoration of tight junction proteins andsuppressed the lipopolysaccharide (LPS)‑mediated hepaticmacrophage activation and pro‑inflammatory response. Inaddition, rifaximin prevented skeletal muscle mass atrophyand weakness by decreasing intramuscular myostatin andpro‑inflammatory cytokine levels. Moreover, rifaximinsynergistically enhanced the L‑carnitine‑mediated improvementof skeletal muscle wasting by promoting the productionof insulin‑like growth factor‑1 and mitochondrial biogenesis,resulting in the inhibition of the ubiquitin‑proteasome system(UPS). The in vitro assays revealed that L‑carnitine directlyattenuated the impairment of mitochondrial biogenesis,thereby inhibiting the UPS in rat myocytes that were stimulatedwith LPS or tumor necrosis factor‑α. On the whole, thepresent study demonstrates that the combination of rifaximinwith L‑carnitine may provide a clinical benefit for livercirrhosis‑related sarcopenia.
博士（医学）・甲第863号・令和5年3月15日
© Murata et al. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.
identifier:International journal of molecular medicine Vol.50 No.2 Article No.101 (2022 Aug)
identifier:11073756
identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4095
identifier:International journal of molecular medicine, 50(2): Article No.101
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2023-12-05T21:41:08+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション