川芎嗪对胶原性关节炎大鼠血清炎性因子与关节滑膜组织的影响  

Effect of Tetramethylpyrazine on Inflammatory Cytokines in Serum and Joint Synovial Tissues in Rats with Collagen-induced Arthritis

作　　者：芦琨[1] 蒋建平[1] 郭辉[1] 李宜川[1] 

机构地区：[1]商丘医学高等专科学校生物化学与分子生物学教研室,商丘476100

出　　处：《医药导报》2016年第2期144-148,共5页Herald of Medicine

基　　金：河南省商丘市2013年科技发展计划项目(20135006)

摘　　要：目的观察川芎嗪(TMP)对胶原性关节炎(CIA)大鼠血清白细胞介素(IL)-8、IL-12、IL-33水平和关节滑膜组织基质金属蛋白酶10(MMP-10)、核因子κB(NF-κB)的影响,探讨其对类风湿关节炎可能的治疗机制。方法将大鼠随机分为正常对照组(n=10)、模型对照组、地塞米松组、川芎嗪小剂量组和川芎嗪大剂量组,每组9只。除正常对照组外,其他组采用Ⅱ型胶原诱导CIA大鼠模型。地塞米松组肌内注射地塞米松2 mg·kg-1,川芎嗪小剂量组和大剂量组分别给予川芎嗪50,100 mg·kg-1。采用足趾容积、关节炎指数评价关节炎症;酶联免疫吸附法测定各组血清IL-8、IL-12、IL-33的水平;Western-blot检测关节滑膜组织MMP-10、NF-κB的表达。结果与模型对照组比较,川芎嗪大剂量组和地塞米松组大鼠足爪肿胀度和关节炎指数明显下降,大鼠血清IL-8、IL-12、IL-33水平和关节滑膜组织MMP-10、NF-κB的表达显著降低,差异有统计学意义(P<0.01)。川芎嗪小剂量组除对足爪肿胀度和血清IL-8、IL-33水平明显抑制外,其他指标差异无统计学意义(P>0.05)。结论大剂量川芎嗪对大鼠CIA有明显的抑制作用,其机制可能是通过平衡促炎细胞因子和抗炎细胞因子的效应,改善大鼠免疫功能障碍,降低关节滑膜炎症,减轻关节软骨的破坏,从而发挥治疗作用。Objective To observe the effect of tetramethylpyrazine（ TMP） on serum interleukin 8（ IL-8）,interleukin12（ IL-12） and interleukin 33（ IL-33） levels and MMP-10 and NF-κB protein expression in joint synovial tissues in rats with collagen-induced arthritis（ CIA）,and further to investigate the mechanism for treating rheumatoid arthritis. Methods Rats were randomly divided into normal control group（ n = 10）,model control group,dexamethasone group,low-dose of TMP and highdose of TMP groups（ n = 9 each）. The CIA model was established in all the groups except for the normal control group. Rats of dexamethasone group were given 2 mg·kg- 1of dexamethasone; Rats of low-dose and high-dose of TMP group were given 50,100 mg·kg- 1of TMP,respectively. The toe volume and arthritis index（ AI） were used to evaluate joint inflammation. The levels of IL-8,IL-12 and IL-33 in the serum of rats were detected by ELISA. The expression levels of MMP-10 and NF-κB in joint synovial were detected by Western blotting. Results Compared with model control group,the toe volume and AI were significantly reduced in high-dose of TMP groups and dexamethasone groups,and levels of IL-8,IL-12 and IL-33 and the expression levels of MMP-10 and NF-κB were decreased significantly（ P〈 0. 01）. TMP（ 50 mg · kg- 1） could obviously decrease the toe volume and the levels of IL-8 and IL-33. There was no statistical difference in other indices（ P〉 0. 05）.Conclusion TMP at 100 mg·kg- 1showed obvious inhibition on CIA rats. The mechanism may be correlated to balancing the effect of proinflammatory factor and anti-inflammatory cytokines,improving immune function in rats,reducing joint synovial inflammation,and alleviating the destruction of the articular cartilage.

关 键 词：川芎嗪 关节炎 胶原性 细胞因子 基质金属蛋白酶10 白细胞介素 

分 类 号：R965.5[医药卫生—药理学]