腹腔注射三氧化二砷对胶原诱导关节炎大鼠血清炎性趋化因子的影响  

Effect of Serum Chemotactic Factor on Collagen Induced Arthritis Rats after Intraperitoneal Injection of Arsenic Trioxide

作　　者：任丽民[1] 张莉芸[2] 张改连[2] 许珂[2] 高晋芳[2] 

机构地区：[1]山西医科大学研究生院,太原030001 [2]山西医科大学附属大医院风湿免疫科,太原030001

出　　处：《中华临床免疫和变态反应杂志》2015年第4期256-261,共6页Chinese Journal of Allergy & Clinical Immunology

基　　金：国家自然科学基金(81202356)

摘　　要：目的评估腹腔注射三氧化二砷(arsenic trioxide,ATO)对胶原诱导关节炎(collagen induced arthritis,CIA)大鼠关节症状的改善程度,并观察其对CIA大鼠血清趋化因子的影响并探讨其可能作用机制。方法将28只体质量及鼠龄相当的Wistar大鼠随机分成3组,A组为空白对照组(8只),B、C组(各10只)用牛Ⅱ型胶原和弗氏完全佐剂乳化液2次免疫动物,建立CIA大鼠模型,造模成功后随机分为CIA模型对照组8只(B组)、ATO治疗组8只(C组);ATO治疗组在分组3 d后通过腹腔注射ATO液1周,剂量为每天4 mg/kg,最后l d给8 mg/kg,观察3 d取材,对照组以同样方法给予等容量的0.9%氯化钠注射液。对各组大鼠定期进行关节炎指数(arthritis index,AI)评定、容积法(排水法)测量双后肢的足肿胀度以及四肢关节X线摄片评估关节破坏程度。各组老鼠干预结束后内眦静脉取血,用流式细胞术对各组大鼠血清正常T细胞表达分泌的活性调节蛋白(regulated upon activation,normal T cell expressed and secreted,RANTES)、单核细胞趋化因子(monocyte chemotactic factor,MCP)-1、干扰素γ诱导蛋白10(interferon gamma induced protein 10,IP-10)等趋化因子进行定量测定。应用t检验或对各组应用Kruskl-Wallis H检验进行组间比较。结果腹腔注射ATO液1周后大鼠足肿胀度较同期CIA模型对照组明显改善,差异有统计学意义[(5.13±0.10)ml vs.(8.12±0.15)ml,t=8.73,P=0.000)];关节炎指数显著降低,差异有统计学意义[(2.63±0.92)vs.(6.62±0.91),t=5.21,P=0.020];X线检查显示关节破坏程度减轻。CIA模型对照组血清中RANTES、MCP-1、IP-10均明显高于同期空白对照组,差异有统计学意义[(8 118.89±2 836.14)pg/ml vs.(5 390.24±629.08)pg/ml,χ2=6.35,P=0.012;22 048.2(6 092.53,40 457.13)pg/ml vs.1 211.77(532.35,1 506.94)pg/ml,χ2=11.29,P=0.001;(282.48±273.93)pg/ml vs.(31.96±17.50)pg/ml,χ2=5.84,P=0.016]。ATO治疗组与同期CIA模型组相比上述因子均明显降低,差异有统计学意�Objective To assess the improvement of articular symptoms on collagen induced arthritis（ CIA） ratsafter intra-peritoneal injection of arsenic trioxide（ ATO） and observe its effect on seral chemotactic factors in CIA rats. Methods Twenty-eight Wistar rats with comparable body weight and age were divided into three groups randomly into： the blank control group（ A,n = 8）,established CIA model group B and C（ n = 20） by immune twice with bovine type Ⅱ collagen and freund＇s complete adjuvant emulsion. The CIA model rats were randomly divided into the CIA model control group B（ n = 8） and the ATO treatment group C（ n = 8） after the successful built up of the CIA model. Three days After grouping,the ATO treatment group were injected with ATO liquid intraperitoneally for 1 week（ dose of 4 mg/g/d,and 8 mg/kg for the last day）. Serum were collected after 3 days. Same amount of normal saline solution were injected to the the control mice with the same approach. Arthritis index（ AI）,degree of foot swelling were evaluated on regularly for each rat and X-ray radiography was used to assess limbs joint damage. Flow cytometry（ FMC）was used to quantitatively detect the chemokines levels of each rats,including regulating normal T cell expressed and secreted（ RANTES）,monocyte chemotactic factor（ MCP）-1,and interferon gamma induced protein 10（ IP-10）. According to the data distribution,t test or Kruskl-Wallis H test was used to compare the parameters between each group. Results（ 1） After 1 week administration of ATO,the foot swelling degree and arthritis index of group C reduced significantly than the CIA model group [（ 5. 13 ± 0. 10） ml vs.（ 8. 12 ± 0. 15） ml,t = 8. 73,P = 0. 000;（ 2. 63 ± 0. 92） vs.（ 6. 62 ± 0. 91）,t = 5. 21,P = 0. 020]at the same period and X-ray showed joint damage was alleviated.（ 2） The serum levels of RANTES,MCP-1,IP-10 in the CIA model group were significantly higher than the blank control group [（ 8 118. 89 ±2 836. 14） pg/m

关 键 词：三氧化二砷 趋化因子 胶原诱导关节炎大鼠 作用机制 

分 类 号：R593.22[医药卫生—内科学]