髓鞘少突胶质细胞糖蛋白35~55肽段诱导C57BL/6 小鼠实验性自身免疫性脑脊髓炎疾病表型

doi:10.16098/j.issn.0529-1356.2020.04.002

解剖学报 ›› 2020, Vol. 51 ›› Issue (4): 483-490.doi: 10.16098/j.issn.0529-1356.2020.04.002

髓鞘少突胶质细胞糖蛋白35~55肽段诱导C57BL/6 小鼠实验性自身免疫性脑脊髓炎疾病表型

蒙延筱楚兰* 徐竹邵冰朱俊羽丹珍卓玛

贵州医科大学附属医院神经内科，贵阳 550004

收稿日期:2020-01-15 修回日期:2020-03-27 出版日期:2020-08-06 发布日期:2020-08-06
通讯作者: 楚兰 E-mail:chulan8999@163.com
基金资助:
国家自然科学基金

Induced experimental autoimmune encephalomyelitis shows the different phenotype of disease in C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55

MENG Yan-xiao CHU Lan* XU Zhu SHAO Bing ZHU Jun-yu Danzhenzhuoma

Department of Neurology of the Affiliated Hospital of Guizhou Medical University, Guiyang 550004，China

Received:2020-01-15 Revised:2020-03-27 Online:2020-08-06 Published:2020-08-06
Contact: CHU Lan E-mail:chulan8999@163.com
Supported by:
National Natural Science Foundation of China

摘要/Abstract

摘要：

目的利用6～8周龄雌性C57BL/6小鼠建立实验性自身免疫性脑脊髓炎（EAE）模型，并对其疾病表型进行探讨，以期建立更接近多发性硬化（MS）的动物模型。方法通过皮内注射髓鞘少突胶质细胞糖蛋白（MOG）35~55肽段免疫50只雌性C57BL/6小鼠，建立EAE模型。每日按15分评分评估其疾病进展情况，观察90 d，进一步通过病理学观察小鼠脑组织病变情况。结果 EAE模型小鼠疾病表现为慢性病程（3只）、复发缓解病程（7只）和单相病程（11只）。部分小鼠（28只）虽然神经功能评分为0，但它们的毛色、精神和活动都发生了变化，在其脑组织中也观察到了炎性脱髓鞘病变。结论用C57BL/6雌性小鼠建立的EAE模型表现出与MS相似的疾病表型，可作为研究MS的良好动物模型。

关键词: 实验性自身免疫性脑脊髓炎, 髓鞘少突胶质细胞糖蛋白35~55肽, 疾病表型, 皮内注射, 小鼠

Abstract:

Objective To establish an experimental autoimmune encephalomyelitis (EAE)model in female C57BL/6 mice aged 6-8 weeks and investigate its disease phenotype so as to build a better animal model of multiple sclerosis (MS). Methods The EAE model was established in 50 female C57BL/6 mice through intradermal injection of myelin oligodendrocyte glycoprotein 35-55 peptide. We assessed the disease progression daily according to a 15-point score for 90 days, and further observed the brain lesions in terms of pathology. Results There were three courses of disease in the EAE model: chronic course (3 mice), relapse and remission course (7 mice) and monophasic course (11 mice). Interestingly, we identified some mice (28 mice) had changes in coat color, mental and motor activity, as well as inflammatory demyelinating lesions in the brain tissue although their neurological functions were scored as 0 point. Conclusion The EAE model in C57BL/6 female mice shows disease phenotype similar to multiple sclerosis and can be used as a good animal model.

Key words: Experimental autoimmune encephalomyelitis, Myelin oligodendrocyte glycoprotein35-55, Disease phenotypes, Intradermal injection, Mouse

中图分类号:

R741.02

蒙延筱楚兰徐竹邵冰朱俊羽丹珍卓玛. 髓鞘少突胶质细胞糖蛋白35~55肽段诱导C57BL/6 小鼠实验性自身免疫性脑脊髓炎疾病表型[J]. 解剖学报, 2020, 51(4): 483-490.

MENG Yan-xiao CHU Lan XU Zhu SHAO Bing ZHU Jun-yu Danzhenzhuoma. Induced experimental autoimmune encephalomyelitis shows the different phenotype of disease in C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55[J]. Acta Anatomica Sinica, 2020, 51(4): 483-490.

参考文献

［1］ Hasselmann J, Karim H, Khalaj AJ, et al. Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice for the longitudinal study of pathology and repair［J］. J Neurosci Methods, 2017,284:71-84.

［2］ Yasuda T, Tsumita T, Nagai Y, et al. Experimental allergic encephalomyelitis (EAE) in mice. Ⅰ. Induction of EAE with mouse spinal cord homogenate and myelin basic protein［J］. Jpn J Exp Med, 1975,45(5):423-427.

［3］ Constantinescu CS, Farooqi N, O’Brien K, et al. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)［J］. Br J Pharmacol, 2011,164(4):1079-1106.

［4］ Bittner S, Afzali AM, Wiendl H, et al. Myelin oligodendrocyte glycoprotein (MOG35-55) induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice［J］. J Vis Exp, 2014, (86): 51275.

［5］ Kennedy MK, Clatch RJ, Dal Canto MC, et al. Monoclonal antibody-induced inhibition of relapsing EAE in SJL/J mice correlates with inhibition of neuroantigenspecific cell-mediated immune responses［J］. J Neuroimmunol, 1987,16(3):345-364.

［6］ Krishnamoorthy G, Saxena A, Mars LT, et al. Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis［J］. Nat Med, 2009,15(6):626-632.

［7］ Weaver A, Goncalves DSA, Nuttall RK, et al. An elevated matrix metalloproteinase (MMP) in an animal model of multiple sclerosis is protective by affecting Th1/Th2 polarization［J］. FASEB J, 2005,19(12):1668-1670.

［8］ Robinson AP, Harp CT, Noronha A, et al. The experimental autoimmune encephalomyelitis (EAE) model of MS: utility for understanding disease pathophysiology and treatment［J］. Handb Clin Neurol, 2014,122:173-189.

［9］ Kishore A, Kanaujia A, Nag S, et al. Different mechanisms of inflammation induced in virus and autoimmune-mediated models of multiple sclerosis in C57BL6 mice［J］. Biomed Res Int, 2013,2013:589048.

［10］ Schmitz K, de Bruin N, Bishay P, et al. R-flurbiprofen attenuates experimental autoimmune encephalomyelitis in mice［J］. EMBO Mol Med, 2014,6(11):1398-1422.

［11］ Dal Monte M, Cammalleri M, Locri F, et al. Fatty acids dietary supplements exert anti-inflammatory action and limit ganglion cell degeneration in the retina of the EAE mouse model of multiple sclerosis［J］. Nutrients, 2018,10(3): 325.

［12］ Reynders T, D’Haeseleer M, De Keyser J, et al. Definition, prevalence and predictive factors of benign multiple sclerosis［J］. eNeurological Sci, 2017,7:37-43.

［13］ Li L，Qiao D，Li Q，et al. Activation, proliferation and regulation of CD8-+T cells stimulated by bacillus calmette-guerin ［J］. Chinese Journal of Immunology, 2011,27 (3): 195-199.(in Chinese)

李丽, 乔丹, 李琴, 等. 卡介苗刺激后CD8～+T细胞活化、增殖及其调节［J］. 中国免疫学杂志, 2011,27(3):195-199.

［14］ Wang YY,Zhang Y,Qin XY, et al. Establishment and evaluation of modified Wistar rat EAE model［J］. Chinese Laboratory Diagnostics, 2012,16 (1): 8-11. (in Chinese)

王彦月, 张艳, 秦新月, 等. 改良Wistar大鼠EAE模型的建立及其评价［J］. 中国实验诊断学, 2012,16(1):8-11.

［15］ Li X,Zhang XCh,Xie GL. Research progress of pertussis toxin［J］. Chinese Journal of Biologicals, 2018, 31 (2): 215219, 224. (in Chinese)

李鑫, 张新创, 谢贵林. 百日咳毒素的研究进展［J］. 中国生物制品学杂志, 2018,31(2):215219, 224.

［16］ Wei ZhW, Zheng PG, Li FG. Preliminary study on the mechanism of soluble MOG35-55 peptide in preventing experimental autoimmune encephalomyelitis ［J］. Practical Clinical Journal of Integration of Traditional Chinese and Western Medicine, 2019,19 (9): 170-172. (in Chinese)

魏忠伟, 郑配国, 李付广. 可溶性MOG35-55多肽预防实验性自身免疫性脑脊髓炎机制的初步研究［J］. 实用中西医结合临床, 2019,19(9):170-172.

［17］Meng RL, Xie Y, Zhang Y, et al. Clomastine promotes remyelination in mice with experimental autoimmune encephalomyelitis ［J］. Tianjin Medicine, 2019,47 (8): 819-823. (in Chinese)

孟仁亮, 谢阳, 张瑶, 等. 氯马斯汀促进实验性自身免疫性脑脊髓炎小鼠的再髓鞘化［J］. 天津医药, 2019,47(8):819-823.

［18］ Afraei S, Sedaghat R, Zavareh FT, et al. Therapeutic effects of pegylated-interferon-alpha2a in a mouse model of multiple sclerosis［J］. Cent Eur J Immunol, 2018,43(1):9-17.

［19］ Milewski M, Manser K, Nissley BP, et al. Analysis of the absorption kinetics of macromolecules following intradermal and subcutaneous administration［J］. Eur J Pharm Biopharm, 2015,89:134-144.

［20］ Zhang L, Xie H, Cui L. Activation of astrocytes and expression of inflammatory cytokines in rats with experimental autoimmune encephalomyelitis［J］. Exp Ther Med, 2018,16(6):4401-4406.

[1]	何可可李远迪文廷浩朱婕高杰胡蓉韩锋苏敏. 红细胞膜相关蛋白通过IL-6/STAT3/ROR-γt 信号通路抑制小鼠实验性自身免疫性脑脊髓炎中Th17细胞分化[J]. 解剖学报, 2023, 54(5): 538-545.
[2]	张沂洲李莎米世雄左洪春张倩倩李晗琳雷梓晗张东泽崔慧先. 雌二醇经雌激素受体调控分拣蛋白相关受体A对小鼠海马神经元树突棘密度和突触蛋白表达的影响[J]. 解剖学报, 2023, 54(3): 261-268.
[3]	曾学晴杨彬周鑫袁婧谢志艳李威万炜刘志文曹文宇. 右美托咪定通过抑制脊髓星形胶质细胞活化改善甲醛诱导的急性炎性痛[J]. 解剖学报, 2021, 52(5): 681-685.
[4]	徐纪伟杨常青陈小平陈旭东范文娟. 宫内缺氧减缓小鼠普肯耶细胞发育和降低小脑肽的表达[J]. 解剖学报, 2021, 52(3): 344-351.
[5]	李威刘志文曾佳玉曾学晴袁婧钟小林万炜. 海马小胶质细胞在小鼠慢性炎性痛所致负性情绪中的形态变化[J]. 解剖学报, 2021, 52(3): 352-357.
[6]	李倩高杰胡蓉韩锋李红苏敏. 磷脂酰肌醇-3激酶/蛋白激酶B/FoxO1信号通路和白细胞介素17在小鼠实验性自身免疫性脑脊髓炎中的表达变化[J]. 解剖学报, 2021, 52(3): 358-364.
[7]	王月静张萌郎尉雅张海燕廉洁冯化杰孙丽慧. 上调锌指和含BTB 域20表达对APPswe/PSE9转基因阿尔茨海默病小鼠学习记忆能力的影响[J]. 解剖学报, 2021, 52(3): 365-369.
[8]	曲明娟郑煜李延敏宋洋王蕾周菊华. 靶向叉头框蛋白J2的CRISPR/Cas9基因敲除质粒的构建及其对肝癌细胞转化生长因子β/Smads表达和增殖的影响[J]. 解剖学报, 2021, 52(2): 231-236.
[9]	张雅雯高莹孙菡聪张皓云王凤斌 . 铁转运相关蛋白在肌萎缩性侧索硬化症转基因鼠脊髓中的表达变化[J]. 解剖学报, 2021, 52(2): 161-167.
[10]	吴奇王顺和程霄向玥陈粼波汪子玲肖含先之姜蓉王璐王亚平. 神经干细胞衰老与核因子E2相关因子2/抗氧化反应元件信号通路的关系[J]. 解剖学报, 2020, 51(6): 815-820.
[11]	马冬雪高维娟贺小平许力军刘亚磊董贤慧. 淫黄葛复合剂对阿尔茨海默病小鼠行为学和海马解聚素金属蛋白酶10表达的影响[J]. 解剖学报, 2020, 51(6): 821-826.
[12]	荆海军周播江. 过氧化物酶体增殖物激活受体δ在原代小鼠成肌细胞分化过程中对肌球蛋白重链亚型的影响[J]. 解剖学报, 2020, 51(5): 765-771.
[13]	郎尉雅刘忠锦张海燕孙丽慧朱坤杰. 表没食子儿茶素没食子酸酯对APP/PS1双转基因小鼠神经元突触可塑性和神经细胞黏附分子表达的影响[J]. 解剖学报, 2020, 51(4): 495-501.
[14]	张宇毛海峰彭瑞. 规律有氧运动促进梗阻性黄疸小鼠肠黏膜紧密连接蛋白Claudin-1的表达及激活C型鸟苷酸环化酶通路有利于损伤的修复[J]. 解剖学报, 2020, 51(4): 588-594.
[15]	王朋白兆荣史茜雯李倩魏中秋刘岩安海娟孙影. 硫氧环蛋白过氧化物酶1对硅沉着病小鼠肺功能的影响[J]. 解剖学报, 2020, 51(4): 583-587.

髓鞘少突胶质细胞糖蛋白35~55肽段诱导C57BL/6 小鼠实验性自身免疫性脑脊髓炎疾病表型

Induced experimental autoimmune encephalomyelitis shows the different phenotype of disease in C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价