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姜黄素对大鼠非酒精性脂肪性肝炎模型肝损伤的减轻作用:一种由Nrf2激活介导的效应?

Liver injury attenuation by curcumin in a rat NASH model: an Nrf2 activation-mediated effect?

作者信息

Li B, Wang L, Lu Q, Da W

机构信息

Department of Gastroenterology, Jiaxing Second Hospital, 1518 North Ring Road, Jiaxing, 314000, Zhejiang, People's Republic of China.

Department of Gastroenterology, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yi Shan Road, Shanghai, 200233, People's Republic of China.

出版信息

Ir J Med Sci. 2016 Feb;185(1):93-100. doi: 10.1007/s11845-014-1226-9. Epub 2014 Nov 11.

Abstract

AIM

Nuclear factor-erythroid 2-related factor-2 (Nrf2) acts as a defense system in the development of nonalcoholic steatohepatitis (NASH). Curcumin is a phenolic compound with lipid regulatory, anti-oxidative, anti-inflammatory and anti-tumorigenic properties that is beneficial in defending against NASH and was recently proved to be an Nrf2 activator. The aim of this study was to evaluate whether Nrf2 activation could be involved in NASH mitigation by curcumin.

METHODS

Hepatic, metabolic, and inflammatory parameters, along with hepatic Nrf2 protein expression were explored in adult Sprague-Dawley rats developing high-fat-diet-induced NASH and submitted to curcumin gavage for 6 weeks.

RESULTS

Curcumin administration led to lower degrees of hepatic steatosis and inflammation; lower levels of serum aminotransferases, lipids, and homeostasis model assessment of insulin resistance; and lower serum and hepatic contents of tumor necrosis factor-α (TNF-α), interleukin-6, and malondialdehyde. In contrast, higher hepatic contents of glutathione, heme oxygenase-1 and superoxide dismutase were observed in rats with curcumin. Moreover, Nrf2 expression in liver cell nuclei was significantly higher in rats with curcumin.

CONCLUSIONS

Curcumin can prevent and ameliorate NASH via lipid reduction, improve insulin resistance, improve anti-inflammatory, and have antioxidant effects, possibly related to its activation of Nrf2.

摘要

目的

核因子红系2相关因子2(Nrf2)在非酒精性脂肪性肝炎(NASH)的发生发展过程中发挥防御系统的作用。姜黄素是一种具有脂质调节、抗氧化、抗炎和抗肿瘤特性的酚类化合物,对抵御NASH有益,且最近被证明是一种Nrf2激活剂。本研究的目的是评估Nrf2激活是否参与姜黄素对NASH的缓解作用。

方法

在成年Sprague-Dawley大鼠中诱导高脂饮食性NASH,并给予姜黄素灌胃6周,探讨肝脏、代谢和炎症参数以及肝脏Nrf2蛋白表达情况。

结果

给予姜黄素可减轻肝脏脂肪变性和炎症程度;降低血清转氨酶、脂质水平以及胰岛素抵抗的稳态模型评估值;降低血清和肝脏中肿瘤坏死因子-α(TNF-α)、白细胞介素-6和丙二醛的含量。相反,给予姜黄素的大鼠肝脏中谷胱甘肽、血红素加氧酶-1和超氧化物歧化酶的含量更高。此外,给予姜黄素的大鼠肝细胞核中Nrf2表达显著更高。

结论

姜黄素可通过降低脂质、改善胰岛素抵抗、抗炎及抗氧化作用预防和改善NASH,这可能与其激活Nrf2有关。

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