黄芩苷通过核因子-κB 通路抑制胶原诱导性关节炎大鼠模型的形成。
Inhibitory effect of baicalin on collagen-induced arthritis in rats through the nuclear factor-κB pathway.
机构信息
Department of Laboratory Diagnosis (H.-Z.W., Y.-H.L.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Departments of Laboratory Diagnosis (H.-Z.W., G.-Z.W.,), Department of Respiratory Medicine (H.Z.), and Department of Orthopaedic Surgery (D.W.), The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China; College of Medical Laboratory Science and Technology and the Key Laboratory of Molecular Diagnosis in Laboratory Medicine (H.-H.W., S.-S.H., Z.-G.W.), and Department of Pharmacology (Y.-G.C.), Harbin Medical University, Daqing, China.
Department of Laboratory Diagnosis (H.-Z.W., Y.-H.L.), The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Departments of Laboratory Diagnosis (H.-Z.W., G.-Z.W.,), Department of Respiratory Medicine (H.Z.), and Department of Orthopaedic Surgery (D.W.), The Fifth Affiliated Hospital of Harbin Medical University, Daqing, China; College of Medical Laboratory Science and Technology and the Key Laboratory of Molecular Diagnosis in Laboratory Medicine (H.-H.W., S.-S.H., Z.-G.W.), and Department of Pharmacology (Y.-G.C.), Harbin Medical University, Daqing, China
出版信息
J Pharmacol Exp Ther. 2014 Aug;350(2):435-43. doi: 10.1124/jpet.114.215145. Epub 2014 Jun 3.
This study focused on the potential therapeutic effect of baicalin on collagen-induced arthritis (CIA) in rats and the underlying mechanisms. The CIA rats were injected with baicalin (50, 100, or 200 mg/kg) once daily for 30 days. The rats were monitored for clinical severity of arthritis, and joint tissues were used for radiographic assessment and histologic examination. We quantified tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in experimental animals and used Western blots to assess levels of protein abundance, phosphorylation, and acetylation of nuclear factor (NF)-κB p65 and sirtuin 1 (sirt1) protein expression in joint tissues. Human fibroblast-like synoviocytes from rheumatoid arthritis (HFLS-RA) were adopted in further mechanistic investigations. Baicalin intraperitoneal injection for 30 days dose-dependently blocked clinical manifestations of CIA, such as functional impairment and swollen red paws. Meanwhile, it alleviated collagen-induced joint inflammation injury and inhibited the secretion of TNF-α and IL-1β in both rat synovium and HFLS-RA. Further mechanistic investigations revealed that baicalin suppresses NF-κB p65 protein expression and phosphorylation in synovial tissue and human-derived synoviocytes. Moreover, the acetylation of NF-κB p65 was downregulated by baicalin, which negatively correlates with the baicalin-induced upregulation of sirt1 expression in the same conditions. The data indicate that CIA in rats can be alleviated by baicalin treatment via relieving joint inflammation, which is related to the suppression of synovial NF-κB p65 protein expression and the elevation of its deacetylation by sirt1.
本研究旨在探讨黄芩素对胶原诱导性关节炎（CIA）大鼠的潜在治疗作用及其机制。CIA 大鼠每日腹腔注射黄芩素（50、100 或 200mg/kg），连续 30 天。监测大鼠关节炎的临床严重程度，对关节组织进行影像学评估和组织学检查。我们检测了实验动物中肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的含量，并通过 Western blot 评估了 NF-κB p65 和 Sirtuin 1（sirt1）蛋白表达的核因子（NF）-κB p65 和 sirt1 蛋白的含量。进一步的机制研究采用了类风湿关节炎（RA）患者的成纤维样滑膜细胞（HFLS-RA）。黄芩素腹腔注射 30 天可剂量依赖性地阻断 CIA 的临床表现，如功能障碍和红肿的爪子。同时，它减轻了胶原诱导的关节炎症损伤，并抑制了大鼠滑膜和 HFLS-RA 中 TNF-α和 IL-1β的分泌。进一步的机制研究表明，黄芩素抑制滑膜组织和人源性滑膜细胞中 NF-κB p65 蛋白的表达和磷酸化。此外，黄芩素还下调了 NF-κB p65 的乙酰化，这与黄芩素在相同条件下诱导 sirt1 表达上调呈负相关。数据表明，黄芩素通过缓解关节炎症减轻大鼠 CIA，这与抑制滑膜 NF-κB p65 蛋白表达和提高其去乙酰化水平有关。
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