三氧化二砷在类风湿关节炎治疗中作用机制的探讨

The mechanisms of As_2O_3 in treating rheumatoid arthritis

目的观察佐剂关节炎(AA)动物模型滑膜组织在诱导凋亡前后的苏木素-伊红(HE)染色及核因子(NF)-κB表达活性的差异,探讨三氧化二砷(As_2O_3)在治疗类风湿关节炎(RA)的可能作用机制。方法将Wistar大鼠造模成功后随机分为两组：AA模型组和As_2O_3治疗组。治疗组每日于发病鼠腹腔注射As_2O_3连续1周,观察3d全部动物处死取材。再经固定、脱钙、包埋,制成切片。然后进行HE染色及免疫组织化学检测。结果HE染色光镜下观察：与正常对照组相比,AA模型组大鼠的滑膜细胞层次增多,6～8层,排列紊乱,有大量炎性细胞浸润；而As_2O_3治疗组可达3～4层,但仍有炎性细胞浸润。免疫组织化学检测结果：AA模型组大鼠关节滑膜的NF-κB(p65)的阳性染色强度明显高于正常对照组,以胞核染色为深,有的成团块状。而As_2O_3治疗组滑膜的NF-κB表达及活性明显下调,但未恢复到正常对照组水平,平均灰度值计算结果显示三组之间差异有统计学意义(P＜0．05)。结论As_2O_3可以抑制分化,诱导滑膜细胞凋亡．而抑制NF-κB的活性和表达可能是As_2O_3发挥治疗作用的重要机制。

Objective To explore the possible mechanisms of Arsenic Trioxide in treating rheumatoid arthritis （RA） by observing the changes of HE staining and NF-KB expression as well as the apoptosis of synoviocytes in adjuvant-induced arthritis rats. Methods After the animal model was set up on Wistar rats suecessfully, they were randomly divided into AA model group and arsenic trioxide treatment group. The treatment group were injected with 4 mg. kg^-1. d^-1 arsenic trioxid fluid for 7 days. All of the rats were killed 3 days after the complete of injections. The joint specimens were exposed, fixed, decalcified, wrapped and cut into slices. All slices were examined by HE stain and immunohistological evaluation. Results HE staining showed that when compared with the normal control group, the layers of synoviocytes of the AA group were increased to 6-8, and the arrangement of synoviocytes was disordered and heavy inflammatory cell infiltration were found in the AA group. In the arsenic trioxide treatment group, the layers of synoviocytes increased to 3-4, and medium amount of inflammatory cell infiltration were found. The intensity of synovial NF-κB （p65） positive stain in AA model group was significantly higher than that in the normal control group. The synovial expression and activation of NF-κB in the treatment group were decreased markedly, and did not return to normal level . The average gray scale calculation showed that there were significant differences between the three groups （P〈0.05）. Conclusions Arsenic trioxide can inhibit synoviocytes differentiation and induce synoviocytes apoptosis. Inhibition of the synovial expression and activation of NF-κB maybe an important mechanism of arsenic trioxide in treating RA.