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川芎嗪通过 Sirt1/NF-κB 和 Nrf-2/HO-1 通路减轻关节炎大鼠模型中的炎症和氧化应激。

Ligustrazine attenuates inflammation and oxidative stress in a rat model of arthritis via the Sirt1/NF-κB and Nrf-2/HO-1 pathways.

机构信息

Department of Rheumatology and Immunology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.

出版信息

Arch Pharm Res. 2019 Sep;42(9):824-831. doi: 10.1007/s12272-018-1089-0. Epub 2018 Nov 17.

DOI:10.1007/s12272-018-1089-0
PMID:30448958
Abstract

Inflammation responses and oxidative stress are closely involved in the pathogenesis of arthritis. Ligustrazine (Lig), a natural four methyl which is isolated from Chinese herb ligusticum chuanxiong hort, has been proved significantly anti-inflammation and anti-oxidative stress effects. The present study aimed to evaluate the effect of Lig on inflammation and oxidative stress in Freund's complete adjuvant (FCA)-induced arthritis in rats. The treatment of Lig significantly decreased the hind-paw volume change and alleviated the histopathological changes in sections of rat paws induced by arthritis. Lig also reduced the serum levels of pro-inflammatory cytokines (interleukin [IL]-6, IL-1 beta, and tumor necrosis factor-alpha), increased the activity of superoxide dismutase (SOD) and reduced the concentration of malondialdehyde (MDA). Besides that, the protein expressions of the sirtuin 1 (Sirt1)/nuclear factor kappa B (NF-κB) and nuclear factor (erythroid-derived 2)-like-2 factor (Nrf-2)/heme oxygenase (HO)-1 pathways determined by western bolt further confirmed that Lig effectively inhibited the Sirt1/NF-κB pathway and activated the Nrf-2/HO-1 pathway. Taken together, our results suggest Lig has therapeutic potential for arthritis, which might be via the regulation of Sirt1/NF-κB and Nrf-2/HO-1 pathways.

摘要

炎症反应和氧化应激与关节炎的发病机制密切相关。川芎嗪(Lig)是从中国草药川芎中分离出来的一种天然四甲基化合物,已被证明具有显著的抗炎和抗氧化应激作用。本研究旨在评估 Lig 在弗氏完全佐剂(FCA)诱导的关节炎大鼠中的抗炎和抗氧化应激作用。 Lig 的治疗显著降低了后爪体积变化,并减轻了关节炎大鼠爪节段的组织病理学变化。 Lig 还降低了促炎细胞因子(白细胞介素[IL]-6、IL-1β和肿瘤坏死因子-α)的血清水平,增加了超氧化物歧化酶(SOD)的活性,降低了丙二醛(MDA)的浓度。此外,通过 Western blot 确定的 Sirtuin 1(Sirt1)/核因子 kappa B(NF-κB)和核因子(红细胞衍生 2)样 2 因子(Nrf-2)/血红素加氧酶(HO)-1 途径的蛋白表达进一步证实,Lig 能有效抑制 Sirt1/NF-κB 途径,激活 Nrf-2/HO-1 途径。综上所述,我们的研究结果表明 Lig 具有治疗关节炎的潜力,其可能通过调节 Sirt1/NF-κB 和 Nrf-2/HO-1 途径。

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