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吴茱萸碱通过 ROS/TXNIP/NLRP3 通路对痛风性关节炎的作用。

Effects of evodiamine on ROS/TXNIP/NLRP3 pathway against gouty arthritis.

机构信息

TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, No.39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China.

Department of Urology/Andrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, People's Republic of China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Feb;397(2):1015-1023. doi: 10.1007/s00210-023-02654-8. Epub 2023 Aug 9.

DOI:10.1007/s00210-023-02654-8
PMID:37555854
Abstract

Evodiamine (EVO) was tested on acute gouty arthritis rats to investigate its anti-inflammatory effect. Seventy-two male Sprague-Dawley (SD) rats were randomly assigned into the control, model, high, medium, and low dose of EVO groups and colchicine group. The ankle swelling degrees were measured at 2 h, 6 h, and 24 h following sodium urate injection into ankle joint. Histopathological examination was performed 24 h after injection. Reactive oxygen species (ROS) content in the ankle joint was detected using chemical fluorescence. Serum interleukin-1β (IL-1β), interleukin-18 (IL-18), and tumor necrosis factor-α (TNF-α) content were determined by ELISA. Serum xanthine oxidase (XOD), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined by spectrophotometry. The expressions of thioredoxin-interacting protein (TXNIP), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), pro-caspase-1, caspase-1, and apoptosis-related spot like protein (ASC) in synovium were detected by Western blot. Evodiamine alleviated the ankle swelling of the affected foot in gouty arthritis rats and reduced inflammatory cell infiltration in joint synovial tissue. Evodiamine also decreased the content of serum inflammatory factors including IL-1β, IL-18, and TNF-α, and increased serum SOD activity, while it decreased serum XOD, MDA activity, and ROS level. Moreover, evodiamine downregulated the protein expression levels of TXNIP, NLRP3, pro-caspase-1, cleaved caspae-1, and ASC. The mechanism of EVO in treating gouty arthritis is associated with the inhibition of NLRP3 inflammasome by regulating the ROS/TXNIP/NLRP3 signaling pathway.

摘要

吴茱萸碱(EVO)在急性痛风性关节炎大鼠中进行了测试,以研究其抗炎作用。72 只雄性 Sprague-Dawley(SD)大鼠随机分为对照组、模型组、高、中、低剂量 EVO 组和秋水仙碱组。尿酸钠注入踝关节后 2h、6h 和 24h 测量踝关节肿胀程度。注射后 24h 进行组织病理学检查。使用化学荧光法检测踝关节中活性氧(ROS)含量。通过 ELISA 测定血清白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)和肿瘤坏死因子-α(TNF-α)含量。通过分光光度法测定血清黄嘌呤氧化酶(XOD)、超氧化物歧化酶(SOD)和丙二醛(MDA)。Western blot 检测滑膜中硫氧还蛋白相互作用蛋白(TXNIP)、NOD 样受体热蛋白结构域相关蛋白 3(NLRP3)、前胱天蛋白酶-1、胱天蛋白酶-1 和凋亡相关斑点样蛋白(ASC)的表达。吴茱萸碱减轻痛风性关节炎大鼠受累足的踝关节肿胀,减少关节滑膜组织中的炎性细胞浸润。吴茱萸碱还降低了血清炎症因子(包括 IL-1β、IL-18 和 TNF-α)的含量,增加了血清 SOD 活性,同时降低了血清 XOD、MDA 活性和 ROS 水平。此外,吴茱萸碱下调了 TXNIP、NLRP3、前胱天蛋白酶-1、切割的胱天蛋白酶-1 和 ASC 的蛋白表达水平。EVO 治疗痛风性关节炎的机制与通过调节 ROS/TXNIP/NLRP3 信号通路抑制 NLRP3 炎性体有关。

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本文引用的文献

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Traditional Chinese medicine for anti-Alzheimer's disease: berberine and evodiamine from .用于抗阿尔茨海默病的中药:来自……的小檗碱和吴茱萸碱
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