Zhang S, Huang G, Yuan K, Zhu Q, Sheng H, Yu R, Luo G, Xu A
School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.
State Key Laboratory of Biocontrol, Department of Biochemistry, School of Life Sciences, Sun Yat-Sen (Zhongshan) University, Guangzhou, Guangdong, China.
Clin Exp Immunol. 2017 Oct;190(1):29-39. doi: 10.1111/cei.12993. Epub 2017 Jul 3.
Rheumatoid arthritis (RA) is a chronic immune inflammatory disease mediated by the influx of immune cells into the synovial joint space. As Tanshinone IIA (TIIA) has potent anti-oxidant and anti-inflammatory activities, we used the adjuvant-induced arthritis (AA) murine model of RA to investigate the impact of TIIA on RA and immune cell activation. The anti-arthritic activity of TIIA was investigated in an adjuvant-induced arthritis model of RA in mice. Myeloperoxidase and neutrophil elastase expression levels were assessed in ankle joints by immunohistochemistry analysis. Immune cell infiltration was evaluated in air pouch experiments. Proinflammatory cytokines expression levels were determined by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays. Neutrophil extracellular traps (NETs) were assessed by immunostaining and confocal microscopy. Treatment with TIIA alleviated cartilage erosion and neutrophil infiltration in the ankle joints of AA mice and reduced proinflammatory cytokine expression levels in sera. TIIA suppressed interleukin-6 and tumour necrosis factor-α expression and release in neutrophils and promoted neutrophil apoptosis. TIIA also inhibited the NET formation of neutrophils. Our findings demonstrated that TIIA can ameliorate RA effectively by targeting neutrophils, indicating that TIIA may act as a potential therapeutic for RA.
类风湿关节炎（RA）是一种慢性免疫炎症性疾病，由免疫细胞流入滑膜关节腔介导。由于丹参酮IIA（TIIA）具有强大的抗氧化和抗炎活性，我们使用RA的佐剂诱导性关节炎（AA）小鼠模型来研究TIIA对RA和免疫细胞活化的影响。在小鼠RA的佐剂诱导性关节炎模型中研究了TIIA的抗关节炎活性。通过免疫组织化学分析评估踝关节中髓过氧化物酶和中性粒细胞弹性蛋白酶的表达水平。在气袋实验中评估免疫细胞浸润。通过定量实时聚合酶链反应（PCR）和酶联免疫吸附测定法测定促炎细胞因子的表达水平。通过免疫染色和共聚焦显微镜评估中性粒细胞胞外陷阱（NETs）。用TIIA治疗可减轻AA小鼠踝关节的软骨侵蚀和中性粒细胞浸润，并降低血清中促炎细胞因子的表达水平。TIIA抑制中性粒细胞中白细胞介素-6和肿瘤坏死因子-α的表达和释放，并促进中性粒细胞凋亡。TIIA还抑制中性粒细胞的NET形成。我们的研究结果表明，TIIA可以通过靶向中性粒细胞有效改善RA，表明TIIA可能作为RA的潜在治疗药物。
