TGF-β1对慢性EAE模型C57BL/6小鼠脑和脾脏Foxp3 mRNA表达影响的研究

Effect of TGF-β1 on the Expression of Foxp3 mRNA in Brains and Spleens of Chronic Experimental Autoimmune Encephalomyelitis Model in C57BL/6 Mice

[目的]观察外源性转化生长因子β1（TGF-β1）对慢性实验性变态反应性脑脊髓炎（EAE）C57BL／6小鼠脑和脾脏Foxp3 mRNA表达的影响。[方法]72只C57BL／6小鼠，随机分为致病组（A组）、干预组（B组）、佐剂对照组（C组）、干预对照组（D组）。各组小鼠取发病初、发病高峰和慢性期不同时间点分为1、2、3亚组。用盲法每天观察动物行为活动，称体重并按Benson评分标准做EAE严重性的临床评估，RT-PCR技术观察各组各期脑和脾组织Foxp3 mRNA的表达变化。[结果]A1～3组平均Benson标准评分分别为2．3±0．4分、3．9±0．5分、3．5±0．4分，B1～3组Benson标准评分2．7±0．4分、4．3±0．5分、2．8±0．5分。A组和B组评分有统计学差异（P〈0．05）。D组为假干预组，D1～D3组，平均Benson标准评分分别为2．4±0．5分、4．0±0．4分、3．6±0．3，与A组无统计学差异（P〉0．05），而与B组有统计学差异（P〈0．05）。佐剂对照组Benson标准评分为0分。致病组和干预组小鼠脑和脾Foxp3在发病初期表达下降，高峰期下降明显，相比有统计学差异（P〈0．05），到慢性期上升，与高峰期相比有统计学差异（P〈0．01）。假干预组Foxp3各时期表达与致病组无统计学差异（P〉0．05），表达变化同致病组。干预组小鼠脑和脾Foxp3表达在发病初期就已下降，但与致病组和假干预组没有统计学差异。在发病高峰期下降较致病组和假干预组明显，并有统计学差异（P〈0．05），在慢性期较致病组表达上升，并有统计学差异（P〈0．01）。[结论]外源性TGF-β1对慢性EAE产生较复杂的影响，高峰期可以使Foxp3表达进一步下调，症状加重，但在慢性期可使Foxp3表达明显上调．从而促进病情缓解。

[Objective]To investigate the effect of TGF-β1 （transforming growth factor-β1） on the changes of Foxp3mRNA expression in brains and spleens of induced chronic non-remitting model of experimental autoimmune encephalomyelitis （EAE）. [Methods] Seventy two adult female C57BL/6 mice were randomly divided into the adjuvant-control group, EAE group, TGF-β1 treatment group and adjuvant treatment-control group. MOG35-55 and CFA were injected subcutaneously in EAE groups. Animals in TGF-β1 treatment groups received TGF-β1 subcutaneous injection in addition to immunization. PBS was injected subcutaneously in adjuvant treatment-control group. At the onset, peak and chronic stage, the group mice were sacrificed. The expression of Foxp3mRNA in brains and spleens were detected by RT-PCR. [Results]The expression of Foxp3 mRNA of brains or spleens in the EAE group or the adjuvant treatment-control group decreased at early time, followed by a descent in the peak phase and increased in the chronic phase（ P 〈0.05） . In TGF-β1 treatment group, the expression of Foxp3 mRNA dramatically deceased （ P 〈0.05） in the peak phase and increased dramatically in the chronic phase （ P〈0.05） in contrast to the EAE group or the adjuvant treatment-control group. [Conclusion] Exogenous TGF-β1 can exert a complex effect on the EAE model. Mice in TGF-β1 treatment group may develop more progressive symptoms and be more prone to recover than those in the EAE group and adjuvant treatment-control group.