L-カルニチンとアンギオテンシン-II1型受容体遮断薬の組み合わせは、非アルコール性脂肪肝炎ラットモデルにおける肝線維症に有益な効果を有する

Inflammation and oxidative stress contribute to the progression of nonalcoholic steatohepatitis (NASH). Hepatic fibrosis and activated hepatic stellate cells (Ac-HSCs) are attenuated by Angiotensin-II type 1 Receptor Blocker (ARB), and L-carnitine is effective for NASH by ameliorating oxidative stress, but neither agent is effective in a clinical setting. We evaluated the effect of the combination of L-carnitine and ARB on liver fibrosis using a rat NASH model. A Choline-Deficient/L-Amino Acid-defined (CDAA) diet was fed to F344 rats for 8 weeks. The rats were then divided into a control group, group receiving L-carnitine or ARB alone, and group receiving L-carnitine plus ARB. Therapeutic efficacy was assessed by evaluating liver fibrosis, liver fatty acid metabolism, and oxidative stress. ARB inhibited liver-specific tumor necrotic factor-α and LPS-binding protein, which are involved in hepatic inflammation. L-Carnitine reduced hepatic oxidative stress by rescuing hepatic sterol-regulatory elementbinding protein 1 and thiobarbituric acid reactive substances induced by the CDAA diet. Combination of L-carnitine and ARB improved liver fibrosis, with concomitant HSC suppression. Therefore, we suggest that L-carnitine and ARB are effective in suppressing liver fibrosis. Currently both drugs are in clinical use, and a combination of the two could be an effective therapy for NASH fibrosis.
博士（医学）・甲第736号・令和2年3月16日
Copyright © 2019 Hideto Kawaratani, Biomed J Sci & Tech Res. This is an openaccess article distributed under the terms of the Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/).