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槲皮素通过抑制 IKK/NF-κB 和 MAPK 信号通路对 LPS/d-GalN 诱导的小鼠急性肝损伤的保护作用。

Hepatoprotective effect of quercetin against LPS/d-GalN induced acute liver injury in mice by inhibiting the IKK/NF-κB and MAPK signal pathways.

机构信息

College of Pharmaceutical Sciences, Southwest University, Chongqing, China.

College of Animal Science and Technology, Southwest University, Chongqing, China.

出版信息

Int Immunopharmacol. 2017 Nov;52:281-289. doi: 10.1016/j.intimp.2017.09.022. Epub 2017 Oct 12.

DOI:10.1016/j.intimp.2017.09.022
PMID:28963941
Abstract

Quercetin is regarded as a potential hepatoprotective agent in the treatment of acute liver injury. However, the underlying mechanism of how quercetin to protect against lipopolysaccharides/d-galactosamine (LPS/d-GalN) induced acute liver injury remains unclear. To investigate the mechanism, the antioxidative, anti-inflammatory and antiapoptotic responses were performed. The results showed that quercetin pretreatment improved the survival rate and substantially reduced the liver histopathological changes in mice. It also alleviated the hepatic damage and reduced the productions of oxidative markers induced by LPS/d-GalN. In addition, quercetin pretreatment significantly diminished the production of inflammatory cytokines, including TNF-α, IL-6 and IL-1β, and inhibited the activation of the NF-κB and MAPK signaling pathways as well as the expression of apoptotic-related proteins induced by LPS/d-GalN. We found that the potential mechanism of this quercetin-induced protection is mainly mediated through its powerful antioxidative capacity, inhibition of hepatocyte apoptosis and suppression of inflammatory cytokines through the IKK/NF-κB and MAPK signaling pathways. Thus, quercetin shows a promising therapeutic effect on acute liver injury in mice.

摘要

槲皮素被认为是治疗急性肝损伤的一种有潜力的肝保护剂。然而,槲皮素如何防止脂多糖/半乳糖胺(LPS/d-GalN)诱导的急性肝损伤的潜在机制尚不清楚。为了研究其机制,进行了抗氧化、抗炎和抗凋亡反应。结果表明,槲皮素预处理提高了小鼠的存活率,并显著减少了肝组织病理学变化。它还减轻了 LPS/d-GalN 诱导的肝损伤和氧化标记物的产生。此外,槲皮素预处理显著减少了 TNF-α、IL-6 和 IL-1β 等炎症细胞因子的产生,并抑制了 LPS/d-GalN 诱导的 NF-κB 和 MAPK 信号通路的激活以及凋亡相关蛋白的表达。我们发现,槲皮素诱导保护的潜在机制主要是通过其强大的抗氧化能力、抑制肝细胞凋亡以及通过 IKK/NF-κB 和 MAPK 信号通路抑制炎症细胞因子来介导的。因此,槲皮素对小鼠急性肝损伤显示出有希望的治疗效果。

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