李宜川 刘国玲 芦琨 常景芝 刘青 郭娅丽

【摘 要】目的：观察川芎嗪（TMP）对胶原性关节炎（CIA）大鼠滑膜组织细胞的增殖、凋亡及滑膜组织中p53表达的影响，并进一步探讨其治疗类风湿关节炎的可能机制。方法：将50只SD大鼠随机分为正常对照组10只和模型组40只。模型组采用Ⅱ型胶原诱导大鼠CIA模型，36只大鼠造模成功。将造模成功的36只大鼠随机分为模型对照组、地塞米松组、TMP高剂量组和TMP低剂量组，每组9只。正常对照组和模型对照组给予2 mL·kg-1生理盐水肌肉注射，地塞米松组给予地塞米松2 mg·kg-1肌肉注射，TMP高剂量组肌肉给药TMP 100 mg·kg-1，TMP低剂量组肌肉给药TMP 50 mg·kg-1。观察

CIA大鼠足肿胀度与关节炎指数，MTT法检测TMP对CIA大鼠足关节滑膜细胞增殖的影响，碱性磷酸酶标记法检测CIA大鼠足关节滑膜细胞凋亡，免疫组化法检测CIA大鼠足关节滑膜细胞p53表达。结果：TMP高剂量组大鼠足爪肿胀程度峰值降低，关节炎指数下降（P < 0.01）；TMP（100 mg·kg-1）可抑制CIA大鼠关节滑膜细胞的增殖，增高大鼠滑膜细胞凋亡积分（P < 0.01），明显降低p53表达（P < 0.01）。结论：TMP（100 mg·kg-1）可抑制CIA大鼠的足爪肿胀和多发性关节炎，对CIA大鼠具有明顯的治疗作用；其机制可能是通过降低CIA大鼠滑膜细胞p53的异常表达水平，促进滑膜细胞凋亡，抑制关节滑膜细胞增殖，减轻局部慢性炎症反应，从而对CIA大鼠发挥治疗作用。

【关键词】 关节炎，类风湿；胶原诱导性；川芎嗪；滑膜细胞；增殖；凋亡；p53；大鼠

【ABSTRACT】Objective：To observe the effect of tetramethylpyrazine（TMP）on the proliferation，apoptosis of synovial cells and the expression of p53 in synovial tissue of rats with collagen induced arthritis and further explore its possible mechanism in the treatment of rheumatoid arthritis.Methods：Fifty SD rats were randomly divided into a normal control group（10 rats）and a model group（40 rats）.The model group was induced by type Ⅱ collagen to establish 36 CAI rat models which then were randomly divided into a model control group，a dexamethasone group，a high-dose TMP group and a low-dose TMP group，with 9 rats in each.The normal control group and the model control group were given an intramuscular injection of 2 mL·kg-1 of physiological saline.The dexamethasone group was given an intramuscular injection of 2 mg·kg-1 of dexamethasone.The high-dose TMP group and the low-dose TMP group were medicated to muscles respectively 100 mg·kg-1 and 50 mg·kg-1of TMP.The foot swelling and arthritis index of the CIA rats were observed.MTT method was used to detect the influence of TMP on the proliferation of synovial cells of CIA foot joints.Alkaline phosphatase labeling was used to detect the apoptosis of synovial cells in the foot joints of CIA rats.The immunohistochemistry method was used to detect the expression of p53 in the synovial cells in foot joints of CIA rats.Results：The paw swelling peak and arthritis index decreased in the high-dose TMP group（P < 0.01）；TMP（100 mg·kg-1）could inhibit the proliferation of synovial cells in CIA rats，increase apoptosis integral of synovial cells（P < 0.01），and significantly reduce the expression of p53（P < 0.01）.Conclusion：TMP（100 mg·kg-1）can inhibit the paw swelling of CIA rats and polyarthritis and has an obvious therapeutic effect on CIA rats，whose treating mechanism may be through reducing the abnormal expression of p53 in synovial cells of CIA rats，promoting apoptosis of synovial cells，inhibiting synovial cell proliferation and reducing the local chronic inflammation reaction.

【Keywords】 arthritis，rheumatoid；collagen inducibility；tetramethylpyrazine；synovial cells；proliferation；apoptosis；p53；rats

类风湿关节炎（rheumation arthritis，RA）是以晨僵、关节肿痛、活动受限为主要临床表现，以关节滑膜为靶器官的自身免疫性疾病，以慢性滑膜炎、滑膜细胞增生、骨质与软骨破坏为主要病理特征，最终导致受累关节发生畸形而出现关节废用、致残，严重影响患者的生活质量。……