聚肌胞苷酸及地塞米松诱导的胸腺萎缩及胸腺RLR信号通路表达的比较研究

Comparison of polycytidylic acid-induced and dexamethasone-induced thymic atrophy and their thymic expression of RIG-Ⅰ like receptors signaling pathway

目的:比较聚肌胞苷酸Poly(I:C)、地塞米松(DEX)对小鼠胸腺的影响和RLR通路的改变,为研究病毒感染导致胸腺受损的机制,选择合适的动物模型提供实验依据。方法:将24只8周龄C57BL/6小鼠随机分组,分别给予Poly(I∶C)、DEX及生理盐水。观察胸腺指数、胸腺组织学变化、外周血中T细胞受体重排删除环(TRECs)的含量以及初始型CD4+T细胞的比例,并检测胸腺组织RLR/MAVS/IFN-α/β通路的表达情况。结果:Poly(I∶C)和DEX都可以导致胸腺萎缩和组织结构破坏,DEX组更严重且皮质区细胞减少更为明显。两组的TRECs均下降。Poly(I∶C)组的初始型CD4+T细胞有增加趋势;而DEX组的CD4^+T细胞初始/记忆亚群比例改变不明显。DEX组RIG-Ⅰ、MDA5、LGP2和IFN-α/β表达上调明显;而Poly(I∶C)组虽略有上调、但无统计学意义。结论:两种造模方法均可诱导胸腺功能受损。DEX诱导的胸腺损伤更严重且伴有RLR——Ⅰ型IFN通路的大幅上调;而在Poly(I∶C)组该通路仅轻微上调。

Objective:To provide experimental evidences for choosing murine models in the pathogenesis research of thymic impairment induced by viral infection,we compared the impacts of polycytidylic acid(Poly(I∶C))and dexamethasone(DEX)on the thymic morphology and thymic output function,and explored the implication of RLR signaling pathway.Methods:24 male C57BL/6 mice were randomly assigned into three groups and treated with Poly(I∶C),DEX,or saline respectively.Thereafter,their thymic morphology,pathological changes,thymic index,and thymic pathology were examined.Their contents of T-cell receptor excision circles(TRECs)and proportions of the naive CD4+T cell in the peripheral blood were determined to evaluate their thymic output function.The expression levels of thymic RLR/MAVS/IFN-α/βsignaling pathway and IL-1βwere also measured.Results:Both Poly(I∶C)and DEX treatment caused thymic atrophy in appearance and structural destruction under the microscope inspection,and DEX treatment did much more severe damage,especially to the thymic cortex.TRECs decreased significantly in both groups.The proportions of na ve/memory CD4+T cell subsets remained stable,though total CD4+T cell decreased in DEX group,while the proportion of na ve CD4+T cell in Poly(I∶C)group increased significantly.The expression of RIG-Ⅰ,MDA5,LGP2,and IFN-α/βwere up-regulated in DEX group,while it remained unchanged in Poly(I∶C)group.Conclusion:Both Poly(I∶C)and DEX induced thymic atrophy and the impaired thymic output function.Nevertheless,the expression of RLR-IFN signaling pathway up-regulated more significantly in DEX group instead of in Poly(I∶C)group.These results implied the existence of different pathological manifestations and mechanisms underlying the impaired thymic function in different animal models,as well as impact on na ve/memory CD4+T cell proportions.Our research provides references for choosing animal models in the basic research and drug development for viral infection induced thymic atrophy based on the RLR signaling pathway.