目的 评估腹腔注射三氧化二砷(ATO)对胶原诱导性关节炎(CIA)大鼠关节症状的改善程度,观察其对CIA大鼠血清NF-KB受体活化因子配体(RANKL)、骨保护素(OPG)水平的影响,并探讨其对NF.KB受体活化因子(RANK)/RANKL/OPG系统的作用机制。方法将28只体质量及鼠龄相当的Wistar大鼠依次编号,用随机数字表法选取8只为对照组(A组),剩余20只为造模组(用牛Ⅱ型胶原和弗氏完全佐剂乳化液免疫动物2次,成功建立CIA大鼠模型16只),造模成功后应用随机数字表法将其分为CIA模型对照组8只、三氧化二砷治疗组8只;三氧化二砷治疗组在分组3d后通过腹腔注射三氧化二砷液1周,剂量4mg·kg-1,·d-1,最后1d给予8mg/kg,观察3d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(AI)评定以及四肢关节x线摄片评估关节破坏程度。各组大鼠干预结束后内眦静脉取血,用流式细胞术(FMC)对各组大鼠血清中核RANKL、骨保护素进行定量测定。应用t检验或对各组应用Wilcoxon秩和检验进行组间比较。结果①腹腔注射三氧化二砷液1周后大鼠AI较同期CIA模型组明显改善(分别为2.63±0.92,6.62±0.91),差异有统计学意义(t=8.73,P〈O.01),X线显示关节破坏程度减轻。②CIA模型组血清中RANKL水平明显高于同期空白对照组[1890.70(797.03,10571.94)pg/ml,74.46(29.21,95.37)pg/ml],差异有统计学意义(T=43,P=0.005③三氧化二砷治疗组与同期CIA模型组相比RANKL水平明显降低[44.78(21.41,79.83)pg/ml,1890.70(797.03,10571.94)pg/m1],差异有统计学意义(T=47,P=0.01)。④3组间血清骨保护素水平相当[16.87(6.91,17.64)pg/ml,5.32(3.42,33.14)pg/ml,14.24(6.96,21.86)pg/m1],差异无统计学意义?
Objective To assess the improvement of articular symptoms on collagen induced arthritis (CIA) rats after injecting arsenic trioxide (ATO) intraperitoneal and observe its effects on serum RANKL, OPG on CIA rats and discuss the possible mechanism on RANK/RANKL/OPG system. Methods Numberd twentyeight Wistar rats with correspond weight and age consecutively, then using random number table select 8 rats as blank control group A. Another other 20 as model group (16 wistar rats are established as CIA models by immunized twice with bovine type Ⅱ collagen and Freund's complete adjuvant emulsion). Using ranllm numbor table divided CIA rast into the CIA model control group B (n=8) and ATO treatment group C (n=8) randomly. After grouping for 3 days, ATO treatment group were injected with ATO liquid intraperitoneally for 1 week (dose of 4 mg· g-1d-1, last 1 day raise to 8 mg/kg). Serum were collected after 3 days , while rates in the control group were given same quantity of saline solution with the same method. Arthritis index (AI) and X-ray radiography were assessed for limb joint damage. Flow cytometry (FMC) was used to detect chemokines quantitatively of each rats serum, including Nuclear factor kappa B ligand receptor activation factor/bone protection predominate (RANKL/OPG). According to the data distribution, t test or Wilcoxon test were used to compare the difference between groups. Results (!) After administration with ATO for 1 week arthritis index of group C reduced significantly than the CIA model group (2.63±0.92, 6.62±0.91, t=8.73, P〈0.01), and X-ray showed joint damage alleviated. (2) The serum level of RANKL in the CIA model group was significantly higher than the blank control group [(1 890.70(797.03, 10 571.94) pg/ml, 74.46(29.21, 95.37) pg/ml, T=43, P= 0.005]; (3) The serum level of RANKL in the ATO treatment group was significantly lower than the CIA model group [44.78 (21.41, 79.83), 1 890.70 (797.03,10 571.94), T=47, P=0.01].