来氟米特对胶原性关节炎大鼠CD4CD25调节性T细胞影响.docVIP

来氟米特对胶原性关节炎大鼠CD4CD25调节性T细胞影响 　　摘 要 目的：探讨来氟米特对胶原性关节炎中免疫抑制性CD4+CD25+调节性T细胞的作用。方法：II型胶原诱导Wistar大鼠，建立胶原性关节炎模型；检测关节炎大鼠多发性关节炎评分，每周2次；流式细胞仪检测脾淋巴细胞中CD4+CD25+调节性T细胞的比例；RT-PCR检测脾淋巴细胞中Foxp3 mRNA的表达。结果：与模型组比较，来氟米特（2 mg/kg，灌胃给药15 d）明显降低CIA大鼠多发性关节炎评分。与关节炎模型组比较，药物干预组CD4+CD25+调节性T细胞的比例升高，转录因子Foxp3 mRNA的表达增高。结论：来氟米特具有抑制关节炎大鼠关节肿胀的作用，该作用可能和促进CD4+CD25+Treg产生和增加Foxp3的表达有关。 　　关键词关节炎 来氟米特 CD25 　　中图分类号：R392.5 文献标识码：A 文章编号：1006-1533(2011)11-0548-03 　　 　　Effect of leflunomide on CD4+CD25+ regulatory T cells in collagen-induced arthritis rats* 　　WANG Ting-yu1，LI Jun2，JIN Zhi-gui1，WU Fei-hua1，JIN Jian1，TANG Ting-ting3，4 　　（1. Department of Pharmacy，Shanghai Ninth People’ s Hospital，School of Medicine at Shanghai Jiao Tong University，Shanghai，200011；2. School of Pharmacy，Anhui Medical University，Hefei，230032；3. Shanghai Key Laboratory of Orthopaedic Implant，Shanghai，200011；4. Department of Orthopaedic Surgery，Shanghai Ninth People’ s Hospital，School of Medicine at Shanghai Jiao Tong University，Shanghai，200011） 　　ABSTRACTObjective: To investigate the effect of leflunomide on the immunosuppressive CD4+CD25+ regulatory T cells (CD4+CD25+ Tregs) in collagen-induced arthritis (CIA). Methods: CIA was induced by collagen type II in Wistar rats. Polyarthritis indexes were checked twice a week. Immunofluorescence flow cytometry and RT-PCR were used to determine the proportion of CD4+CD25+ Tregs and the expression of Foxp3 mRNA in the splenocytes of CIA rats，respectively. Results: Leflunomide (2 mg/kg，ig×15 days，day 10-24) could significantly decrease the polyarthritis indexes in CIA rats. Compared with model CIA rats，administration of leflunomide could significantly increase the number ofCD4+CD25+ Tregs and the expression of Foxp3 mRNA in spleen lymphocytes of CIA rats. Conclusions: The results demonstrated that the inhibition of arthritis by leflunomide was related to changes in CD4+CD25+ Tregs. 　　KEY WORDSarthritis；leflunomide；CD25 　　 　　类风湿性关节炎（rheumatoid arthritis, RA）存在着持续性滑膜炎症及进展性软骨和骨破坏