不同剂量MOG35-55对EAE小鼠p-JAK1、BDNF表达的影响

doi:10.3969/j.issn.1006-7795.2014.06.010

首都医科大学学报 ›› 2014, Vol. 35 ›› Issue (6): 725-729.doi: 10.3969/j.issn.1006-7795.2014.06.010

• 神经系统常见病的基础研究 • 上一篇下一篇

不同剂量MOG_35-55对EAE小鼠p-JAK1、BDNF表达的影响

屈赵^1,2, 张丽¹, 李林¹, 王奇², 尹琳琳¹

1. 首都医科大学宣武医院药物研究室神经变性病教育部重点实验室, 北京 100053;
2. 广州中医药大学临床药理研究所, 广州 510405

收稿日期:2014-08-18 发布日期:2014-12-15
通讯作者: 尹琳琳 E-mail:yinll913@126.com
基金资助:
国家自然科学基金项目(81001656,81341088,81273817),首都卫生发展科研专项(首发2011-1001-06),北京市优秀人才培养资助项目 (2012D005018000010)

Expressions of p-JAK1 and BDNF in experimental autoimmune encephalomyelitis in mice induced by myelin oligodendrocyte glycoprotein at different doses

Qu Zhao^1,2, Zhang Li¹, Li Lin¹, Wang Qi², Yin Linlin¹

1. Department of Pharmacology, Xuanwu Hospital, Capital Medical University, Key Laboratory of Neurodegenerative Disease, Ministry of Education, Beijing 100053, China;
2. Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China

Received:2014-08-18 Published:2014-12-15
Supported by:
This study was supported by National Natural Science Foundation of China(81001656, 81341088, 81273817), Capital Medical Development Special Program(2011-1001-06), Beijing Organization Department of Municipal Party Committee Project for Highly Talented Man(2012D005018000010).

摘要/Abstract

摘要：

目的比较不同剂量髓鞘少突胶质细胞糖蛋白35-55(myelin oligodendrocyte glycoprotein 35-55,MOG_35-55)多肽片段免疫诱导C57BL/6小鼠实验性变态反应性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)其磷酸化酪氨酸蛋白激酶 1(phospho-Janus kinase 1,p-JAK1),脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)表达的变化。方法将C57BL/6小鼠采用数字表法随机分为对照组、MOG_35-55 50 μg(MOG-50)组和MOG_35-55 200 μg(MOG-200)组。EAE小鼠分别以每只动物50 μg或200 μg MOG_35-55的抗原皮下多点注射诱导造模,对照组乳剂中不含MOG_35-55。观察各组小鼠的发病率、病死率、体质量、神经功能评分的变化。并用Western blotting法检测酪氨酸蛋白激酶 1(Janus kinase 1,JAK1)及p-JAK1在皮质中的表达情况;免疫组织化学染色的方法检测BDNF在皮质中的表达情况。结果 MOG_35-55 50 μg和200 μg均能成功诱导EAE模型,并增强p-JAK1的表达,减少BDNF的表达。其中MOG-200组在体质量减轻、神经功能评分及p-JAK1表达方面较MOG-50组作用明显,且与对照组相比差异有统计学意义(P<0.05)。结论 MOG-200组p-JAK1、BDNF变化明显,可以作为研究药物干预作用的理想模型。

关键词: 实验性变态反应性脑脊髓炎, 髓鞘少突胶质细胞糖蛋白, 磷酸化酪氨酸蛋白激酶 1(p-JAK1), 脑源性神经营养因子(BDNF)

Abstract:

Objective To compare the expressions of phospho-Janus kinase 1(p-JAK1)and brain-derived neurotrophic factor(BDNF) of experimental autoimmune encephalomyelitis(EAE) in C57BL/6 mice models induced by myelin oligodendrocyte glycoprotein 35-55(MOG_35-55) at different dosages. Methods Thirty female SPF-grade C57BL/6 mice with 18-22 gram body weight were divided randomly into three groups: control group and EAE model groups(MOG_35-55 50 μg dosage group and MOG_35-55 200 μg dosage group). The mice of the two model groups were injected subcutaneously over flanks with the antigen containing 50 μg, 200 μg MOG_35-55/mouse and complete Freund's andjuvant(CFA) in the same volume, respectively. The mice of the control group were injected in the same way phosphate buffered saline(PBS) without containing MOG_35-55; 500 ng pertussis toxin(PTX) in 0.2 mL phosphate buffer solution(PBS) was given by intraperitoneal injection to the mice of the two model groups at 0 and 48 h post-immunization. The mice in control group were injected with PBS in the same way. The disease incidence, death rate, body weight and neurological score of the mice were observed. Meanwhile, the expression of JAK1 and p-JAK1 in cortex were examined by western blotting and brain-derived neurotrophic factor(BDNF) evaluated by immunohistochemical staining. Results The C57BL/6 mouse model of EAE was successfully induced by two different dosages of MOG_35-55. The expression of p-JAK1 in cortex were increased while BDNF decreased. However, the influence of MOG_35-55 200 μg dosage group on loss of weight, neurological score and the expression of p-JAK1 seemed to be more significant than MOG_35-55 50 μg dosage group. Conclusion The mouse model of immune-induced EAE was successfully established with MOG_35-55 200 μg and this EAE mouse model is stable and can be used in the drug research of multiple sclerosis(MS).

Key words: experimental autoimmune encephalomyelitis, myelin oligodendrocyte glycoprotein, phospho-Janus kinase 1, brain-derived neurotrophic factor

中图分类号:

R967

屈赵, 张丽, 李林, 王奇, 尹琳琳. 不同剂量MOG_35-55对EAE小鼠p-JAK1、BDNF表达的影响[J]. 首都医科大学学报, 2014, 35(6): 725-729.

Qu Zhao, Zhang Li, Li Lin, Wang Qi, Yin Linlin. Expressions of p-JAK1 and BDNF in experimental autoimmune encephalomyelitis in mice induced by myelin oligodendrocyte glycoprotein at different doses[J]. Journal of Capital Medical University, 2014, 35(6): 725-729.

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不同剂量MOG_35-55对EAE小鼠p-JAK1、BDNF表达的影响

Expressions of p-JAK1 and BDNF in experimental autoimmune encephalomyelitis in mice induced by myelin oligodendrocyte glycoprotein at different doses

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