中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (1): 78-87.doi: 10.12092/j.issn.1009-2501.2026.01.009
收稿日期:2025-04-14
修回日期:2025-05-26
出版日期:2026-01-26
发布日期:2026-02-13
通讯作者:
余守洋
E-mail:2961667421@qq.com;yusy@zmu.edu.cn
作者简介:施雅妍,女,研究方向:神经胶质细胞功能与疾病研究。E-mail:基金资助:
Yayan SHI1(
), Yu WANG2, Wei KUANG2, Shouyang YU3,*(
)
Received:2025-04-14
Revised:2025-05-26
Online:2026-01-26
Published:2026-02-13
Contact:
Shouyang YU
E-mail:2961667421@qq.com;yusy@zmu.edu.cn
摘要:
多发性硬化症(multiple sclerosis,MS)是一种中枢神经系统(central nervous system,CNS)的慢性炎症性脱髓鞘疾病。多发性硬化症是一个全球性问题,可表现出肌肉无力、无法行走等运动症状以及认知障碍、神经心理症状、疼痛等非运动症状。多发性硬化症的发病机制复杂,涉及自身免疫反应、遗传因素和环境因素等多个方面。近年来,药物治疗仍属于多发性硬化症一线治疗方式。本综述归纳了多发性硬化症可能的发病机制和药物治疗进展,提出了一些未来可能的研究方向,为探讨多发性硬化症发病机制和治疗提供新思路。
中图分类号:
施雅妍, 王钰, 旷炜, 余守洋. 多发性硬化的发病机制和药物治疗的最新进展[J]. 中国临床药理学与治疗学, 2026, 31(1): 78-87.
Yayan SHI, Yu WANG, Wei KUANG, Shouyang YU. The latest progress in the pathogenesis of multiple sclerosis and drug therapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(1): 78-87.
| 多发性硬化模型 | 建模方式 | 应用 | 参考文献 |
| 复发缓解型EAE | 对SJL/J 小鼠皮下注射髓鞘蛋白多肽 PLP139-151以诱导EAE | 复发缓解型多发性硬化 | [ |
| 进行性EAE | 对 C57BL/6J 小鼠皮下注射髓鞘少突胶质细胞糖蛋白肽 MOG35-55 以诱导EAE | 原发性进展型多发性硬化 继发进行型多发性硬化 | [ |
| TEMV诱导的模型 | 将TMEV注射到 SJL/J 小鼠脑内 | 原发性进展型多发性硬化 | [ |
| Cuprizone 诱导的模型 | 用 0.2% Cuprizone喂养 C57BL/6 小鼠 6 周 | 脱髓鞘和髓鞘再生过程 | [ |
| 溶血卵磷脂诱导的模型 | 直接注射1 μL 1%的LPC至C57BL/6小鼠的脑内 | 脱髓鞘和髓鞘再生过程 | [ |
表 1 常用的多发性硬化动物模型
Table 1 Commonly used animal model of multiple sclerosis
| 多发性硬化模型 | 建模方式 | 应用 | 参考文献 |
| 复发缓解型EAE | 对SJL/J 小鼠皮下注射髓鞘蛋白多肽 PLP139-151以诱导EAE | 复发缓解型多发性硬化 | [ |
| 进行性EAE | 对 C57BL/6J 小鼠皮下注射髓鞘少突胶质细胞糖蛋白肽 MOG35-55 以诱导EAE | 原发性进展型多发性硬化 继发进行型多发性硬化 | [ |
| TEMV诱导的模型 | 将TMEV注射到 SJL/J 小鼠脑内 | 原发性进展型多发性硬化 | [ |
| Cuprizone 诱导的模型 | 用 0.2% Cuprizone喂养 C57BL/6 小鼠 6 周 | 脱髓鞘和髓鞘再生过程 | [ |
| 溶血卵磷脂诱导的模型 | 直接注射1 μL 1%的LPC至C57BL/6小鼠的脑内 | 脱髓鞘和髓鞘再生过程 | [ |
图 1 多发性硬化发病机制 缩写:促炎性T辅助1型(T helper type1,Th1);促炎性T辅助17型(T helper type1,Th17);干扰素-γ(interferon gamma,IFN-γ);肿瘤坏死因子-α(tumor necrosis factor alpha,TNF-α);白细胞介素17(interleukin-17,IL-17);活性氧(reactive oxygen species,ROS);活性氮(reactive nitrogen species,RNS);活性羰基(reactive carbonyl species,RCS)。
Fig.1 Pathogenesis of multiple sclerosis
| 药物名称 | 给药途径 | 可治疗的多发性 硬化类型 | 可治疗的其他自身免疫病 | 参考文献 |
| 特立氟胺 | 口服 | RRMS | 活动性类风湿性关节炎 银屑病关节炎 系统性红斑狼疮 系统性血管炎 | [ |
| 富马酸二甲酯 | 口服 | RRMS | 中重度银屑病 | [ |
| 芬戈莫德 | 口服 | RRMS | 克罗恩病 溃疡性结肠炎 银屑病 对哮喘有积极影响 | [ |
| 奥扎莫德 | 口服 | RRMS | 克罗恩病 溃疡性结肠炎 银屑病 | [ |
| 西尼莫德 | 口服 | SPMS | 克罗恩病 溃疡性结肠炎 银屑病 | [ |
| 庞西莫德 | 口服 | RRMS和SPMS | 克罗恩病 溃疡性结肠炎 银屑病 | [ |
| 克拉屈滨 | 口服 | RRMS | 活动性类风湿性关节炎 银屑病关节炎 系统性红斑狼疮 | [ |
| 干扰素 β | 皮下注射 | RRMS和SPMS | 葡萄膜炎 | [ |
| 醋酸格拉替雷 | 皮下注射 | RRMS | 尚不确定 | [ |
| 奥法木单抗 | 皮下注射 | PPMS | MS合并类风湿性关节炎 系统性红斑狼疮 | [ |
| 奥瑞珠单抗 | 静脉注射 | PPMS | MS合并类风湿性关节炎 系统性红斑狼疮 | [ |
| 那他珠单抗 | 静脉注射 | RRMS | 克罗恩病 | [ |
| 阿仑单抗 | 静脉注射 | RRMS和/或对其他治疗选择无反应的多发性硬化患者 | 对难治性肉芽肿性多血管炎、系统性血管炎、活动性和难治性类风湿关节炎、散发性包涵体肌炎有积极影响 | [ |
表 2 已批准用于治疗多发性硬化的药物
Table 2 Approved drugs for multiple sclerosis therapy
| 药物名称 | 给药途径 | 可治疗的多发性 硬化类型 | 可治疗的其他自身免疫病 | 参考文献 |
| 特立氟胺 | 口服 | RRMS | 活动性类风湿性关节炎 银屑病关节炎 系统性红斑狼疮 系统性血管炎 | [ |
| 富马酸二甲酯 | 口服 | RRMS | 中重度银屑病 | [ |
| 芬戈莫德 | 口服 | RRMS | 克罗恩病 溃疡性结肠炎 银屑病 对哮喘有积极影响 | [ |
| 奥扎莫德 | 口服 | RRMS | 克罗恩病 溃疡性结肠炎 银屑病 | [ |
| 西尼莫德 | 口服 | SPMS | 克罗恩病 溃疡性结肠炎 银屑病 | [ |
| 庞西莫德 | 口服 | RRMS和SPMS | 克罗恩病 溃疡性结肠炎 银屑病 | [ |
| 克拉屈滨 | 口服 | RRMS | 活动性类风湿性关节炎 银屑病关节炎 系统性红斑狼疮 | [ |
| 干扰素 β | 皮下注射 | RRMS和SPMS | 葡萄膜炎 | [ |
| 醋酸格拉替雷 | 皮下注射 | RRMS | 尚不确定 | [ |
| 奥法木单抗 | 皮下注射 | PPMS | MS合并类风湿性关节炎 系统性红斑狼疮 | [ |
| 奥瑞珠单抗 | 静脉注射 | PPMS | MS合并类风湿性关节炎 系统性红斑狼疮 | [ |
| 那他珠单抗 | 静脉注射 | RRMS | 克罗恩病 | [ |
| 阿仑单抗 | 静脉注射 | RRMS和/或对其他治疗选择无反应的多发性硬化患者 | 对难治性肉芽肿性多血管炎、系统性血管炎、活动性和难治性类风湿关节炎、散发性包涵体肌炎有积极影响 | [ |
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