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烟酰胺核糖对实验性自身免疫性脑脊髓炎小鼠的神经保护作用研究

Study of neuroprotective effect of nicotinamide riboside on EAE mice

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【作者】 席国萍; 宋国斌; 李艳花; 孟涛; 王记委; 苏琴; 贾思玮; 郭漪; 王青; 马存根;

【Author】 XI Guoping;SONG Guobin;LI Yanhua;MENG Tao;WANG Jiwei;SU Qin;JIA Siwei;GUO Yi;WANG Qing;MA Cungen;Institute of Brain Science, Shanxi Datong University;The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine;

【通讯作者】 王青;马存根;

【机构】 山西大同大学脑科学研究所; 山西中医药大学国家中医药管理局多发性硬化益气活血重点研究室;

【摘要】 目的:探讨烟酰胺核糖(NR)对实验性自身免疫性脑脊髓炎(EAE)小鼠的神经保护作用。方法:采用髓鞘少突胶质细胞糖蛋白(MOG35-55)免疫诱导C57BL/6雌性小鼠制备EAE模型,随机分为EAE组和NR组。从免疫后第3天到免疫后第27天,EAE组小鼠灌胃生理盐水(200μl/d),NR组小鼠灌胃NR(500 mg/kg,200μl/d),每天记录各组小鼠临床评分和体质量。免疫后第28天处死小鼠,提取小鼠脊髓蛋白,制备小鼠脊髓冰冻切片。髓鞘染色检测脊髓髓鞘脱失,免疫荧光染色检测脊髓MAP-2表达及NeuN、BDNF、GDNF、NGF和NT-3阳性细胞数量,Western blot检测脊髓BDNF、GDNF、NGF、NT-3表达。结果:与EAE组相比,NR显著推迟EAE小鼠发病时间(P<0.05),降低临床评分(P<0.05),减少体质量丢失,减轻脊髓髓鞘脱失(P<0.05),促进脊髓MAP-2表达(P<0.01),增加NeuN阳性细胞数量(P<0.01),上调BDNF、GDNF、NGF、NT-3表达(P<0.05)。结论:NR对EAE小鼠表现出良好的神经保护作用,其机制可能与NR显著增加脊髓神经营养因子表达,改善中枢神经系统微环境,营养神经,促进神经修复、神经生长等有关。

【Abstract】 Objective:To investigate the neuroprotective effect of nicotinamide riboside(NR) on experimental autoimmune encephalomyelitis(EAE) mice. Methods:C57BL/6 female mice were induced by myelin oligodendrocyte glycoprotein(MOG35-55) to produce EAE model and were randomly divided into EAE group and NR group. From day 3 to day 27 after immunization, each mouse in EAE group was given normal saline(200 μl/d) and each mouse in NR group was given NR(500 mg/kg, 200 μl/d) by intragastric administration. Clinical score and body weight of mice in EAE group and NR group were recorded every day. On the 28th day after immunization, the spinal cord protein of mice in each group was extracted and the frozen sections of spinal cord of mice in each group were prepared. LFB staining was used to detect demyelination, immunofluorescence staining was used to detect the expression of MAP-2 and the number of positive cells of NeuN, BDNF, GDNF, NGF and NT-3, and Western blot was used to detect the expressions of BDNF, GDNF, NGF and NT-3 of spinal cord. Results:Compared with EAE group, NR significantly delayed the onset time of EAE mice(P<0.05), decreased clinical score(P<0.05), reduced weight loss, alleviated spinal cord demyelination(P<0.05), increased the expression of MAP-2(P<0.01) and the number of NeuN positive cells(P<0.01), and up-regulated the expressions of BDNF, GDNF, NGF and NT-3(P<0.05). Conclusion:NR shows a good neuroprotective effect on EAE mice. The mechanism may be related to NR significantly increasing the expression of spinal neurotrophic factors, improving the microenvironment of the central nervous system, nourishing nerves, promoting nerve repair and nerve growth, etc.

【基金】 国家自然科学基金青年科学基金项目(81903596);山西省基础研究计划项目(202203021211327);山西省重点实验室项目(202105D121011);药用资源与天然药物化学教育部重点实验室开放课题(2019004);山西省卫健委医学科技领军团队项目(2020TD05);山西省卫健委中医药科研课题(2022ZYYC090);国家中医药管理局多发性硬化益气活血重点研究室经费项目;山西中医药大学学科建设经费(2023XKJS-02);老年慢性病智慧医康养大同市重点实验室项目;山西省基础研究计划项目(20210302123475)
  • 【文献出处】 中国免疫学杂志 ,Chinese Journal of Immunology , 编辑部邮箱 ,2025年09期
  • 【分类号】R744.51
  • 【下载频次】58
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