並列タイトル等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
タイトル（掲載誌）International journal of molecular medicine
一般注記type:Thesis
The gut‑liver‑muscle axis is associated with the
development of sarcopenia in liver cirrhosis. The present
study aimed to illustrate the combined effects of rifaximin
and L‑carnitine on skeletal muscle atrophy in cirrhotic rats
with steatohepatitis. For this purpose, a total of 344 Fischer
rats 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 measurements
of psoas muscle mass index and forelimb grip strength
were performed. After feeding for 12 weeks, blood samples,
and liver, ileum and gastrocnemius muscle tissues were
harvested. The effects of L‑carnitine on rat myocytes were
assessed using in vitro assays. Treatment with rifaximin
attenuated hyperammonemia and liver fibrosis in the
CD AA‑fed rats. Moreover, it improved intestinal permeability
with the restoration of tight junction proteins and
suppressed the lipopolysaccharide (LPS)‑mediated hepatic
macrophage activation and pro‑inflammatory response. In
addition, rifaximin prevented skeletal muscle mass atrophy
and weakness by decreasing intramuscular myostatin and
pro‑inflammatory cytokine levels. Moreover, rifaximin
synergistically enhanced the L‑carnitine‑mediated improvement
of skeletal muscle wasting by promoting the production
of 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 directly
attenuated the impairment of mitochondrial biogenesis,
thereby inhibiting the UPS in rat myocytes that were stimulated
with LPS or tumor necrosis factor‑α. On the whole, the
present study demonstrates that the combination of rifaximin
with L‑carnitine may provide a clinical benefit for liver
cirrhosis‑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
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
提供元機関・データベース奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU