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瑞香素通过增强乙醇代谢、抑制氧化应激和调节炎症介质治疗乙醇诱导的大鼠肝纤维化的疗效。

The therapeutic effect of fraxetin on ethanol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and modulating inflammatory mediators in rats.

机构信息

Department of ultrasound imaging, the First Affiliated Hospital of Wenzhou Medical University, China.

Department of Orthopaedic Surgery, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.

出版信息

Int Immunopharmacol. 2018 Mar;56:98-104. doi: 10.1016/j.intimp.2018.01.027. Epub 2018 Feb 2.

DOI:10.1016/j.intimp.2018.01.027
PMID:29414667
Abstract

The present study was designed to investigate the possible protective effects of fraxetin against ethanol induced liver fibrosis in rats. Rats were underwent intragastric administration of ethanol (5.0-9.5 g/kg) once a day for 24 weeks. Effect of fraxetin against ethanol induced liver fibrosis was investigated by giving 20 or 50 mg/kg fraxetin. At the end of experiment, the livers were collected for histopathological analyses, protein extraction, and enzymatic activities. Our results indicated that fraxetin significantly corrected ethanol-induced hepatic fibrosis, as evidenced by the decrease in serum ALT and AST, the attenuation of histopathological changes. Fraxetin also expedited ethanol metabolism by enhancing the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. Besides, fraxetin alleviated lipid peroxidation, enhanced hepatic antioxidant capabilities, inhibited CYP2E1 activity, and reduced the inflammatory mediators, including TNF-α and IL-1β via up-regulation of hemeoxygenase-1 (HO-1) protein. In summary, the hepatoprotection of fraxetin is mostly attributed to its antioxidant capability, alcohol metabolism, and anti-inflammation effect.

摘要

本研究旨在探讨瑞香素对乙醇诱导的大鼠肝纤维化的可能保护作用。大鼠每天经胃内给予乙醇(5.0-9.5 g/kg),共 24 周。通过给予 20 或 50 mg/kg 的瑞香素来研究瑞香素对乙醇诱导的肝纤维化的作用。实验结束时,收集肝脏进行组织病理学分析、蛋白质提取和酶活性测定。我们的结果表明,瑞香素显著纠正了乙醇诱导的肝纤维化,这表现在血清 ALT 和 AST 的降低,组织病理学变化的减轻。瑞香素还通过增强醇脱氢酶(ADH)和醛脱氢酶(ALDH)的活性来加速乙醇代谢。此外,瑞香素通过上调血红素加氧酶-1(HO-1)蛋白减轻脂质过氧化、增强肝抗氧化能力、抑制 CYP2E1 活性,并减少 TNF-α 和 IL-1β 等炎症介质。综上所述,瑞香素的保肝作用主要归因于其抗氧化能力、酒精代谢和抗炎作用。

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