沙利度胺对大鼠佐剂性关节炎的治疗作用及其对炎性细胞因子的影响

Therapeutic potential of thalidomide and its effect in proinflammatory cytokines in adjuvant-induced arthritis rats

目的评价沙利度胺在佐剂性关节炎(AA)大鼠模型中的治疗作用,并探讨其可能的机制。方法随机分为模型对照组、100mg·kg-·1d-1沙利度胺治疗组、200mg·kg-·1d-1沙利度胺治疗组和正常对照组。治疗过程中连续对大鼠的关节炎症程度进行评分。治疗前后对大鼠的右后足进行放射学评分。治疗14d后,检测各组大鼠右膝关节滑膜的组织病理学改变及血清肿瘤坏死因子(TNF)-α和白细胞介素(IL)-1β的水平。结果不同剂量沙利度胺治疗组的关节炎指数、放射学及滑膜组织病理学改变均较模型对照组明显改善(P<0.05),不同剂量沙利度胺治疗组间差异无统计学意义(P>0.05);沙利度胺能显著下调AA大鼠血清TNF-α和IL-1β的水平(P<0.01和0.05),且不同剂量下TNF-α的水平差异有统计学意义(P<0.01),而IL-1β差异无统计学意义(P>0.05)。结论沙利度胺能改善AA大鼠关节炎症状、放射学及滑膜组织病理变化,并能明显降低AA大鼠血清中TNF-α和IL-1β的水平。

Objective To evaluate the therapeutic potential of thalidomide, an immunomodulator, in adjuvant-induced arthritis rats, and to explore its mechanism of action. Methods Rats were randomly divided into a control group, 100 mg·kg^-1·d^-1 thalidomide-treated group, 200 mg·kg^-1·d^-1 thalidomide-treated group and a normal control group. Severity of joint inflammation was examined and scored consecutively during treatment. Right hind limb radiographic changes were scored before and after treatment. After fourteen days＂ treatment, serum levels of tumor necrosis factor （TNF）-alpha and interleukin （IL）-1β and the histopathological changes of synovium in the right stifle-joint were measured in all groups. Results Severity of joint inflammation, score of synovitis and radiographic changes in thalidomide-treated rats were significantly improved compared with control rats （P〈0.05）. There was no significant difference between two doses of thalidomide-treated groups （P〉0.05）. Serum level of TNF-alpha and IL-1β in thalidomide-treated rats was significantly decreased （P〈0.01 and 0.05）, and there was notable difference in level of TNF-alpha between 100 mg·kg^-1·d^-1 and 200 mg·kg^-1·d^-1 thalidomide-treated group （P〈0.01）, but level of IL-1β had no difference （P〉0.05）. Conclusion Thalidomide can remarkably improve adjuvant-induced arthritis of rat and down-regulate serum levels of TNF-alpha and IL-1β.