Department of Rheumatology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
Mol Med Rep. 2017 Nov;16(5):6162-6169. doi: 10.3892/mmr.2017.7389. Epub 2017 Aug 29.
Rheumatoid arthritis is a chronic autoimmune disease characterized by an elevated synovial inflammatory response, with destruction or erosion of articular cartilage in major joints. The aim of the present study was to examine whether 20‑hydroxyecdysone (HES) is able to ameliorate oxidative stress and inflammatory responses in a collagen‑induced rheumatoid arthritis (CIA) rat model. A total of 40 healthy male rats were selected arbitrarily and separated into four groups. Rats treated with saline served as a control (group I), rats subjected to CIA induction by intradermal injection of bovine collagen II type served as the induced group (group II), while rats induced with CIA and administered with 10 and 20 mg/kg bodyweight HES for 28 days served as treatment groups (groups III and IV). Biochemical parameters, including paw swelling (edema), arthritis score, indexes of thymus and spleen, antioxidant levels (superoxide dismutase, catalase and glutathione), articular elastase and anti‑collagen II specific immunoglobulins (Ig)G, IgG1 and IgG2a, in addition to inflammatory markers [nitric oxide, C‑reactive protein, interleukin (IL)‑1β, IL‑6, tumor necrosis factor‑α and nuclear factor‑κB p65 subunit] were significantly decreased (P<0.01) following supplementation with HES (10/20 mg/kg). Consistently, the protein expression pattern of inducible nitric oxide synthase and cyclooxygenease‑2 were significantly downregulated (P<0.01) upon treatment with HES. In addition, histological analysis confirmed arthritis in CIA‑induced rats by revealing the presence of greater polymorphonuclear cell infiltration, with eroded articular cartilage and prominent synovitis. However, administration of HES was demonstrated to alleviate the morphological changes and maintain the normal architecture of synovial joints. In conclusion, the results of the present study indicated that treatment with HES (particularly 20 mg/kg) may effectively eradicate the inflammatory cascade and oxidative stress process in CIA‑induced rats and thereby exhibit anti‑rheumatoid arthritis properties.
类风湿性关节炎是一种慢性自身免疫性疾病，其特征为滑膜炎症反应升高，主要关节的关节软骨遭到破坏或侵蚀。本研究旨在探讨 20-羟基蜕皮甾酮（HES）是否能够改善胶原诱导性类风湿关节炎（CIA）大鼠模型中的氧化应激和炎症反应。
将 40 只健康雄性大鼠任意选择并分为四组。注射牛 II 型胶原诱导 CIA 的大鼠作为诱导组（II 组），接受盐水治疗的大鼠作为对照组（I 组），接受 CIA 诱导且用 10 和 20mg/kg 体重 HES 治疗 28 天的大鼠作为治疗组（III 组和 IV 组）。
生化参数，包括爪肿胀（水肿）、关节炎评分、胸腺和脾脏指数、抗氧化水平（超氧化物歧化酶、过氧化氢酶和谷胱甘肽）、关节弹性蛋白酶和抗胶原 II 特异性免疫球蛋白（Ig）G、IgG1 和 IgG2a，以及炎症标志物[一氧化氮、C 反应蛋白、白细胞介素（IL）-1β、IL-6、肿瘤坏死因子-α和核因子-κB p65 亚单位]在 HES（10/20mg/kg）补充后显著降低（P<0.01）。同样，诱导型一氧化氮合酶和环氧化酶-2 的蛋白表达模式在 HES 治疗后显著下调（P<0.01）。
此外，组织学分析通过揭示存在更多多形核细胞浸润、侵蚀性关节软骨和明显的滑膜炎证实了 CIA 诱导大鼠的关节炎。然而，HES 的给药被证明可以减轻形态变化并维持滑膜关节的正常结构。
总之，本研究结果表明，HES（特别是 20mg/kg）治疗可能有效消除 CIA 诱导大鼠中的炎症级联和氧化应激过程，并表现出抗类风湿关节炎特性。
