组蛋白去乙酰化酶抑制剂TSA对小鼠胶原诱导性关节炎的治疗作用

The protective effects of histone deacetylases inhibitor TSA on the mice model of rheumatoid arthritis

目的 研究组蛋白去乙酰酶化抑制剂制滴菌素A（TSA）对小鼠胶原诱导性关节炎的作用,初步探讨其作用机制.方法 将雄性DBA/1小鼠随机分为胶原诱导性关节炎（CIA）模型组、预防性给药组、治疗性给药组、正常组.免疫后第35天处死小鼠,检测小鼠足爪炎症的肿胀度,病理切片观察炎症变化,MTT法检测脾淋巴细胞对胶原的增殖反应,实时荧光定量PCR检测TSA对小鼠脾细胞IFN-γ、IL-4 mRNA表达的影响,ELISA检测IFN-γ、IL-4的含量.结果 CIA模型组关节炎评分、对CⅡ的增殖反应、IFN-γ水平均高于正常对照组;给药组关节炎评分、对CⅡ的增殖反应低于CIA模型组;给药组IFN-γ水平低于CIA组,但IL-4水平高于CIA组.结论 TSA对CIA具有抑制作用,其可能机制是抑制T细胞的活化、增殖,调节Th1/Th2的失衡状态.

Objective To investigate the effects of trichostatin A（TSA）on the mice model of collagen induced arthritis（CIA）.Methods Mice model of rheumatoid arthritis（RA）was induced in DBA/1 mice with type Ⅱ collagen.Paws were scored for histological severity of arthritis.The severity of inflammation of mouse joint was evaluated by histological examination.Real-time PGR was used to determine the cytokine mRNA expression.Cytokine production was measured by ELISA from serum,spleen cell culture or dendritic cell and T cell co-culture supematant.T cell proliferation was examined by MTT method.Results TSA can significantly suppress the severity of the arthritis in CIA.IFN-γ was elevated in CIA mice,but was inhibited significantly by TSA introduced either at the same time with immunization or at the onset of manifestation of arthritis.Collagen specific T cell proliferation was significantly suppressed by introduction of TSA.Increased level of IL-4 by T cells was observed in TSA treated group compared to that of control group.Conclusion IL-4 level was increased and played a critical role in the protective effects of TSA in CIA.TSA suppresses the progress of CIA by regulates the balance of Th1/Th2 differentiation.