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实验性自身免疫性脑脊髓炎小鼠模型视神经炎发病机制:与辅助性T细胞亚群的关系 被引量:4

Correlation analysis of pathogenesis of optic neuritis with helper T cell subsets in a mouse experimental autoimmune encephalomyelitis model
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摘要 背景:视神经炎的病因多为自身免疫引起的炎性脱髓鞘,很多的视神经炎为多发性硬化的早期表现。在外周CD4+T细胞中,有5%-10%为调节性T细胞,其免疫抑制能力很强。自身免疫性脑脊髓炎所引起的视神经炎发病机制是否与辅助性T细胞亚群的有关呢?目的:分析实验性自身免疫性脑脊髓炎小鼠模型视神经炎发病机制与辅助性T细胞亚群的关系。方法:将小鼠腹腔注射百日咳菌液建立实验性自身免疫性脑脊髓炎模型,分别免疫11,15,19 d,并设腹腔注射生理盐水的佐剂组小鼠作对照。结果与结论:酶联免疫吸附检测显示,与佐剂组相比,免疫后19 d组视神经白细胞介素4蛋白含量降低(P<0.05);免疫后11,15 d组视神经白细胞介素17蛋白含量升高(P<0.05);免疫后15,19 d组视神经干扰素γ蛋白含量升高(P<0.05);免疫后11,15,19 d组视神经Foxp3蛋白含量显著降低(P<0.05)。实时PCR检测显示,与佐剂组相比,免疫后11,15,19 d组视神经中干扰素γ、Foxp3 mRNA表达降低(P<0.05),RORt mRNA表达升高;免疫后15,19 d组视神经中白细胞介素4,白细胞介素17,T-beat mRNA表达升高(P<0.05)。免疫后19 d组GATA3 mRNA表达降低(P<0.05)。结果证实,实验性自身免疫性脑脊髓炎小鼠模型视神经炎的发生发展可能受到Foxp3和调节性T细胞表达减少的影响,免疫后早期白细胞介素17可能介导对炎症损伤,发病高峰期干扰素γ可能使炎症损伤程度加重。 BACKGROUND:More and more evidence have shown that autoimmune-induced inflammatory demyelinating mostly leads to optic neuritis that is quite an early manifestation of multiple sclerosis, but whether the pathogenesis of optic neuritis in experimental autoimmune encephalomyelitis (EAE) mice is correlated with helper T cellsubsets has rarely been reported. OBJECTIVE:To analyze the correlation between pathogenesis of optic neuritis of mouse EAE model with helper T cellsubsets. METHODS:The mice were injected intraperitoneal y Bordetel a pertussis to establish EAE models. Then, the animal models were subjected to immunization for 11, 15, 19 days, respectively. Mice undergoing intraperitoneal injection of normal saline served as controls (adjuvant group). RESULTS AND CONCLUSION:Compared with the adjuvant group, the protein expression of interleukin 4 in the optic nerve decreased in the 19-day immunization group (P〈0.05);the protein expression of interleukin 17 in the optic nerve increased in the 11-and 15-day immunization groups (P〈0.05);the protein expression of interferonγin the optic nerve increased in the 15-and 19-day immunization groups (P〈0.05);the protein expression of Foxp3 in the optic nerve decreased in the 11-, 15-and 19-day immunization groups (P〈0.05). Real-time PCR results showed that compared with the adjuvant group, the mRNA expression of interferonγand Foxp3 in the optic nerve decreased (P〈0.05), while mRNA expression of RORt increased in the 11-, 15-and 19-day immunization groups;the mRNA expression of interleukin 4, interleukin 17, T-beat increased in the 15-and 19-day immunization groups (P〈0.05);the mRNA expression of GATA3 reduced in the 19-day immunization group (P〈0.05). These results reveal that Foxp3 expression and helper T cellreduction have important influences on the development of optic neuritis in EAE mouse models, interleukin 17 may mediates inflammatory injury in the early stage, while interferon-γmakes inflammatory injury worse in the peak incidence of the disease.
出处 《中国组织工程研究》 CAS CSCD 2014年第42期6763-6768,共6页 Chinese Journal of Tissue Engineering Research
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