FTY720对BXSB小鼠自发性系统性红斑狼疮治疗作用的初步研究

目的　观察新型免疫抑制剂FTY72 0对自发性系统性红斑狼疮 (SLE)动物模型BXSB小鼠的治疗作用 ,并用cDNA芯片从基因表达调控角度全局性地初步考察FTY72 0可能作用的免疫通路。方法　BXSB小鼠给予FTY72 0每次 10mg/kg灌胃 ,每周 2次 ;从 9周龄起点动态评估血清IFANA滴度和肾脏组织病理学改变。用cDNA芯片检测脾脏单个核细胞基因表达谱。结果　FTY72 0能够降低处理组BXSB模型血清的IFANA滴度 (P <0 0 5 ) ,FTY72 0对BXSB模型小鼠免疫复合物型肾小球肾炎有明显的抑制作用。脾脏单个核细胞基因表达谱筛选到差异表达基因 2 4 7个 ,包括一批与细胞移行相关的、参与细胞骨架调节的基因。结论　FTY72 0能够对BXSB狼疮模型起到抑制作用。表达谱数据支持FTY72 0主要是通过激活鞘氨醇 1 磷酸 (sphingosine 1 phosphate,S1P)受体从而加速淋巴细胞重新分布的作用机制 ,并提示该通路可能需要Rho蛋白和钙调蛋白参与。FTY72 0可能成为区别于细胞毒免疫抑制剂的新的SLE治疗药物。

Preliminary study of treating BXSB spontaneous lupus model by FTY720

Objective To examine the effects of a novel immunosuppressant,FTY720 on BXSB mouse lupus prone syndrome,and to investingate its immune regulatory pathway by using cDNA microarray.Methods BXSB mice received oral administration of 10 mg/kg FTY720 twice a week from 9 weeks of age.Therapeutic efficacy was evaluated by levels of anti nuclear antibodies (ANA) in serum and the histopathology of the kidney.Expression profile of spleen lymphocyte was analyzed by cDNA microarray.Results FTY720 significantly suppressed the production of ANA ( P < 0 05) and reduced the deposition of IgG in glomeruli compared with control animals.Microarray was used to determine 247 differential expressed genes,which contain a cluster of genes related to lymphocyte trafficking and cytoskeletal remodeling.Conclusion FTY720 can suppress the development of autoimmunity of male BXSB mice.Microarray data support that FTY720 can accelerate lymphocyte homing and redistribution by activating sphingosine 1 phosphate receptor.These data also suggest Rho protein and calmodulin may be critical in this pathway.FTY720 may be a potential therapeutic drug different from traditional cytotoxic agents in treating systemic lupus erythematosus (SLE).