佐剂关节炎大鼠肺功能降低与调节性T细胞减少及Foxp3表达下调相关

The reduced pulmonary function is related to the decreased expression of Treg and Foxp3 in adjuvant-induced arthritis rats

目的观察佐剂关节炎(AA)大鼠肺功能、调节性T细胞(Treg)及其表面标志物-叉头状转录因子(Foxp3)变化,探讨Treg、Foxp3在RA肺病变中的作用。方法将30只大鼠随机分为正常组和模型组,每组15只,向模型组大鼠右后足跖皮内注射弗氏完全佐剂0.1 mL致炎,复制成AA模型。致炎30 d后,观察大鼠足跖肿胀度、关节炎指数,采用动物肺功能仪检测大鼠肺功能,流式细胞术检测大鼠外周血Treg表达,RT-PCR、免疫组化、免疫印迹法检测大鼠肺组织Foxp3 mRNA、Foxp3蛋白表达。结果与正常组比较,AA大鼠组织肿胀度和关节炎指数升高,肺功能参数降低,外周血CD4+CD25+Treg、CD4+CD25+Foxp3+Treg表达降低,同时,肺组织Foxp3 mRNA和Foxp3蛋白表达水平亦降低(P<0.01或P<0.05)。结论 AA大鼠在发生关节炎症的同时,其肺功能水平降低,Treg、Foxp3表达降低,免疫平衡失调。

Objective To observe changes of pulmonary function, regulatory T cells （Treg）, forkhead transcription factor protein 3 （Foxp3） in adjuvant-induced arthritis （AA） rats, and explore the roles of Treg and Foxp3 expression in im- munological mechanisms of AA. Methods Thirty rats were randomly divided into normal control （NC） group and model con- trol （MC） group, with ]5 in each. The rats of MC group were induced by intracutaneous injection of 0.1 mL complete Fre- und＇s adjuvant in the right posterior paw. After 30 d, we observed the changes of the toe swelling degree, arthritis index. Pulmonary function was detected by animal spirometry, Treg in the peripheral blood by flow cytometry, and Foxp3 mRNA and protein by RT-PCR, immunohistochemistry, Western blotting, respectively. Results Compared with the NC group, the toe swelling degree and arthritis index significantly increased, and the parameters of pulmonary function, CD4＋ CD25＋ Treg, CD4＋ CD25＋ FoxP3 ＋ Treg, Foxp3 mRNA and protein levels decreased in the MC group （ P 〈 0. 01 or P 〈 0.05）. Conclusion AA rats suffer from reduced pulmonary function and immune dysfunction, which may be related to the decreased expressions of Trea and FoxD3.