沙利度胺抑制大鼠胶原诱导关节炎滑膜组织缺氧诱导因子-1α的表达  

Thalidomide inhibits the expression of hypoxia-inducible factor-1αin synovial tissues of rats with collagen-induced arthritis

作　　者：吴忠[1] 李晶[1] 

机构地区：[1]江苏大学附属医院风湿科,镇江212001

出　　处：《中华风湿病学杂志》2007年第4期217-220,I0002,共5页Chinese Journal of Rheumatology

摘　　要：目的探讨沙利度胺类风湿关节炎的治疗作用及其与滑膜缺氧诱导因子-1α(HIF-1α)的关系。方法雌性SD大鼠,将其随机分为模型组和正常组,再将两组分别随机分为对照组、溶媒组和沙利度胺治疗组。模型组用Ⅱ型胶原诱导关节炎,沙利度胺组每天600 mg/kg灌胃;溶媒组以相同剂量的溶媒(10%二甲亚砜)灌胃;每天观察大鼠一般情况及炎症大鼠的关节炎指数,16d后麻醉断头处死,评价疗效包括分析腕关节或踝关节的病理变化和关节炎指数,应用Western blot和免疫组织化学方法进一步分析膝关节滑膜组织的HIF-1α蛋白表达的变化。结果与模型组中的对照组比较,沙利度胺治疗组在用药1周后症状明显改善,2周后病理变化有明显改善,关节炎指数明显降低;模型组滑膜组织HIF-1α蛋白表达显著增强(P<0.05),而沙利度胺治疗组显著受到抑制(P<0.05)。结论沙利度胺能明显减轻类风湿关节炎的症状和病理变化,其作用机制可能与抑制滑膜组织HIF-1α蛋白表达有关。Objective To observe the therapeutic effect of thalidomide（Thd） on rheumatoid arthritis and its relation with the expression of hypoxia-inducible factor-1α（HIF-1α）. Methods Female SD rats were randomly divided into two groups： a normal group and a model group. Each group was further divided into three subgroups： the control group, the vehicle group and the Thd group. The model group was subjected to collagen-induced arthritis. The Thd group and the vehicle group were given Thd （600 mg/kg） once daily and its vehicle DMSO respectively. The profile of arthritis was assessed by observing the clinical symptoms and histopathology and a qualitative clinical score of arthritis. The expression of HIF-1α in synovial tissuses was further detected by Western blot and immunohistochemistry technics. Results Compared to the control group with arthritis, clinical signs and pathological changes of arthritis were improved one and two weeks after administration of Thd respectively, and the qualitative clinical score of arthritis was evidently lowered. The expression of HIF-1α in the inflammed synovial tissuses was found to be enhanced （P〈0.05） in the model group without treatment, but significantly inhibited （P〈0.05） in the Thd group. Conclusion The results suggest that Thd can improve the clinical signs and histopathological changes of rheumatoid arthritis. HIF-1α may be highly expressed in the inilammed synovial tissues, which can be inhibited by Thd. The therapeutic effect of Thd on rheumatoid arthritis may be involved in its inhibitory role in HIF-1α expression in the synovium.

关 键 词：大鼠 关节炎 滑膜 缺氧诱导因子-1Α 沙利度胺 

分 类 号：R593.2[医药卫生—内科学]