Anti‑inflammatory effects of oxymatrine on rheumatoid arthritis in rats via regulating the imbalance between Treg and Th17 cells.
Anti‑inflammatory effects of oxymatrine on rheumatoid arthritis in rats via regulating the imbalance between Treg and Th17 cells.
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氧化苦参碱通过调节Treg和Th17细胞失衡对大鼠类风湿性关节炎的抗炎作用
DOI：
10.3892/mmr.2017.6484
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发表时间：
2017-06
影响因子：
3.4
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Ma A;Yang Y;Wang Q;Wang Y;Wen J;Zhang Y
氧化苦参碱（OMT）是从中药苦参中提取的单体生物碱，长期以来被用作治疗炎症性疾病的中药。本研究的目的是研究 OMT 的潜在抗炎作用，及其对胶原诱导性关节炎 (CIA) 大鼠调节性 T (Treg) 细胞和辅助性 T (Th) 17 细胞之间失衡的调节作用。用II型胶原免疫Sprague-Dawley大鼠，第二次胶原免疫后，用OMT或地塞米松(DXM)腹腔注射，每天一次，持续43天。评估爪肿胀、关节炎评分和关节组织病理学。通过使用酶联免疫吸附测定测定炎症反应细胞因子的血清水平来评估 Treg/Th17 介导的自身反应，包括肿瘤坏死因子 (TNF)-α 和白细胞介素 (IL)-17。使用逆转录定量聚合酶链反应分析测定用 II 型胶原刺激的脾细胞中叉头框 P3 (FOXP3) 和视黄酸相关孤儿受体 (ROR)γt 的 mRNA 水平。此外，使用蛋白质印迹分析测量 FOXP3 和 RORγt 的蛋白表达水平。结果表明，OMT 治疗显着降低了 CIA 的严重程度，显着消除了爪子肿胀、关节炎评分和滑膜增生，并增加了体重减轻。 OMT 显着降低 CIA 大鼠 TNF-α 和 IL-17A 的产生，上调 FOXP3 并下调 RORγt。总之，本研究证明OMT通过抑制CIA大鼠炎症和调节Treg/Th17对类风湿性关节炎（RA）发挥保护作用，表明OMT可作为人类RA的免疫抑制和软骨保护药物。
Oxymatrine (OMT), a monosomic alkaloid extracted from the Chinese herb, Sophora flavescens Ait, has long been used as a traditional Chinese medicine for the treatment of inflammatory diseases. The aim of the present study was to investigate the potential anti-inflammatory effect of OMT, and its modulation on imbalance between regulatory T (Treg) cells and T helper (Th) 17 cells in rats with collagen-induced arthritis (CIA). Sprague-Dawley rats were immunized with type II collagen and following a second collagen immunization, the rats were treated with OMT or dexamethasone (DXM) intraperitoneally once a day for 43 days. Paw swelling, arthritic score and joint histopathology were evaluated. The Treg/Th17-mediated autoreactive response was assessed by determining serum levels of inflammatory response cytokines, including tumor necrosis factor (TNF)-α and interleukin (IL)-17, using an enzyme-linked immunosorbent assay. The mRNA levels of forkhead box P3 (FOXP3) and retinoic acid-related orphan receptor (ROR)γt in spleen cells stimulated with type II collagen were determined using reverse transcription-quantitative polymerase chain reaction analysis. In addition, the protein expression levels of FOXP3 and RORγt were measured using western blot analysis. The results showed that OMT treatment significantly reduced the severity of CIA, markedly abrogating paw swelling, arthritic scores and synovial hyperplasia, and the increased loss in body weight. OMT significantly reduced the production of TNF-α and IL-17A, upregulated FOXP3 and downregulated RORγt in rats with CIA. In conclusion, the present study demonstrated that OMT exhibited a protective effect on rheumatoid arthritis (RA) through the inhibition of inflammation and regulation of Treg/Th17 in the CIA rats, suggesting that OMT may be used as an immune suppressive and cartilage protective medicine in human RA.