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辛伐他汀对胶原诱导关节炎大鼠的治疗机制探索

王友莲1,杨明峰1,尚可1,皮慧2   

  1. 1. 江西省人民医院
    2. 南昌大学医学院
  • 收稿日期:2013-06-17 修回日期:2013-09-02 出版日期:2014-01-15 发布日期:2014-01-15
  • 通讯作者: 杨明峰

therapeutic mechanism of simvastatin on rat with collagen induced arthritis

  • Received:2013-06-17 Revised:2013-09-02 Published:2014-01-15 Online:2014-01-15
  • Contact: Ming-Feng YANG

摘要: 目的 以胶原诱导关节炎 (CIA) 大鼠为模型, 观察辛伐他汀对其血清细胞因子及滑膜组织天冬氨酸蛋白水解酶-3 (Caspase-3) 表达的影响, 探索辛伐他汀治疗类风湿关节炎的可能机制。方法 使用牛Ⅱ型胶原建立CIA模型, 将造模成功的大鼠 (16只) 均分为模型组及药物组, 未造模者 (7只) 为对照组。药物组用2.0 mg/ (kg·d) 灌胃, 对照组和模型组用无菌注射用水5 mL/ (kg·d) 灌胃。记录大鼠关节炎评分 (AI) 和足趾容积, 每周1次; 初次免疫后第42天, 眼内眦取血采用ELISA法检测各组血清肿瘤坏死因子 (TNF) -α、 白细胞介素 (IL) -6水平, 处死大鼠取后肢踝关节进行HE染色, 并用免疫组织化学检测滑膜组织Caspase-3表达。结果 药物组和模型组AI在初次免疫后21 d开始下降, 35 d后药物组均低于模型组 (均P<0.05)。2组足趾容积于初次免疫14 d后缓慢下降, 但仍明显高于对照组; 35、 42 d时药物组均低于模型组 (均P<0.05)。初次免疫后42 d, 药物组TNF-α和IL-6水平均低于模型组,高于对照组 (均P<0.05)。药物组较模型组踝关节滑膜组织增生明显减轻, 仅有少量炎细胞浸润, Caspase-3的表达明显上调。结论 辛伐他汀可明显抑制CIA大鼠血清TNF-α、 IL-6的分泌, 上调滑膜组织Caspase-3的表达及减轻滑膜组织增生。

关键词: 辛伐他汀, 关节炎, 抗炎作用, 肿瘤坏死因子α, 白介素6, caspase-3

Abstract: Objective To evaluate therapeutic effects of simvastatin on rat with collagen induced arthritis(CIA) and to supply theoretical basis for exploring new treatments of rheumatoid arthritis. Method Arthritis was induced by injecting bovine Ⅱ collagen into Wistar rat.The rat were randomly divided into three groups: normal control,CIA control,simvastatin groups.Every seven days after first injection record once arthritis index(AI) and the volumes of hind paw; Measure the changes in serum cytokine levels including TNF-α,IL-6 by ELISA and detect the expression of caspase-3 in ankle synovial tissue by immunohistochemical and use HE staining analyse ankle pathological on fortieth day. Results The serum levels of TNF-α,IL-6 and AI and the volumes of hind paw in simvastatin group were decreased on fortieth day.The expression of caspase-3 in simvastatin group was high and synovial hyperplasia was light than that of the CIA control group. Conclusion: simvastatin can decrease serum levels of TNF-α,IL-6 in CIA rat.Also can inhibite synovial hyperplasia and increse the expression of caspase-3 in ankle of the CIA rat.

Key words: simvastatin, arthritis, anti-inflammatory, TNF-α, IL-6, caspase-3