醋酸格拉默别构抑制抗原提呈细胞活化对实验性变态反应性脑脊髓炎大鼠的作用

The treatment of Glatiramer acetate allosteric inhibiting the activation of antigen presenting cell to the EAE model of rats

目的通过对MOG35-55肽段诱导的实验性变态反应性脑脊髓炎(EAE)大鼠模型的研究,探讨醋酸格拉默对别构抑制抗原提呈细胞活化而起到治疗作用的机制。方法利用髓鞘少突胶质细胞糖蛋白35-55(MOG35-55)肽段诱导SD大鼠制作慢性非缓解型EAE模型成功后,随机抽取部分发病模型大鼠,利用醋酸格拉默別构抑制抗原提呈细胞(APC)活化,观察临床体征及组织病理变化情况,同时检测APC重要的免疫相关指标白细胞介素-12(IL-12)、主要组织相容性复合体-1(MHC-Ⅰ)、主要组织相容性复合体-2(MHC-Ⅱ)在大鼠脑内的表达并加以分析评估。结果醋酸格拉默可以抑制EAE大鼠脑内APC活化,下调提呈功能相关的MHC-Ⅰ、MHC-Ⅱ类分子及细胞因子IL-12的表达水平(P <0. 05)。通过大鼠血-脑屏障通透性变化,经醋酸格拉默治疗后未观察到明显变化,较发病高峰期和慢性维持期差异无统计学意义;甲泼尼龙组血-脑屏障通透性有所降低,较与EAE组比较有统计学意义(P <0. 05)。结论醋酸格拉默对大鼠慢性EAE的治疗作用与通过别构抑制APC抗原提呈功能而缓解慢性大鼠EAE神经功能损伤症状有关。

Objective Based on the research of the MOG35-55 peptide-induced EAE model of rats,the mechanism of glatiramer acetate allosteric inhibiting the activation of antigen presenting cell was explored. Methods After produced chronic non-remitting EAE model induced by MOG35-55 peptide,the rats were randomly selected when they were in the peak of onset. GA was used to treat,then the clinical symptom and the immune-related indicators were analyzed in order to evaluate the efficacy of this fusion immunoglobulin to EAE rat. Result GA decreased the activity of the complement system generates fragments and inhibited APC antigen presentation,reduced the expression of MHC,blocked the APC antigen presenting and lymphocyte activation. Conclusion The treament of GA may be related to reducing the APC antigen presenting and ease chronic neurologic injury symptoms of EAE.