淫羊藿苷对cuprizone诱导精神分裂症样小鼠模型行为学变化、髓鞘脱失及神经炎性反应的影响

doi:10.3969/j.issn.1006-7795.2021.05.011

首都医科大学学报 ›› 2021, Vol. 42 ›› Issue (5): 761-767.doi: 10.3969/j.issn.1006-7795.2021.05.011

• 神经精神疾病的中药治疗 • 上一篇下一篇

淫羊藿苷对cuprizone诱导精神分裂症样小鼠模型行为学变化、髓鞘脱失及神经炎性反应的影响

陈溪^1,2, 马登磊¹, 李林^1*

1.首都医科大学宣武医院药学部北京市神经药物工程技术研究中心,北京 100053;
2.北京医药集团职工大学药学系,北京 100079

收稿日期:2021-07-16 发布日期:2021-10-29
通讯作者: 国家自然科学基金(81673406),首都医科大学科研培育项目(PYZ19134),北京市科协青年人才托举计划(2020-2022),北京市金桥种子工程项目(Z191100006119017)。

Effects of icariin on the behavioral changes, demyelination and neuroinflammation in mice with cuprizone-induced schizophrenia

Chen Xi^1,2, Ma Denglei¹, Li Lin^1*

1. Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing Engineering Research Center for Nerve System Drugs, Beijing 100053, China;
2. Department of Pharmacy, Peking Pharmaceutical University of Staffs and Workers, Beijing 100079, China

Received:2021-07-16 Published:2021-10-29
Contact: National Natural Science Foundation of China (81673406), Cultivation Fund of Capital Medical University (PYZ19134), Youth Foundation of Beijing Association for Science and Technology(2020-2022), Beijing Golden-bridge Project(Z21045).

摘要/Abstract

摘要： 目的应用双环己酮草酰二腙(cuprizone)诱导的精神分裂症样小鼠模型,研究淫羊藿苷(icariin,ICA)对模型小鼠行为学变化、髓鞘脱失及神经炎性反应的影响。方法用含0.2%(质量分数) cuprizone的饲料饲喂C57BL/6小鼠5周,制备脱髓鞘模型。造模同时灌胃给予ICA(25、50 mg/kg),持续5周。用Y迷宫和旷场试验进行行为学检测,油红O染色检测髓鞘脱失,免疫组织化学法检测髓鞘碱性蛋白(myelin basic protein, MBP)表达、小胶质细胞和星形胶质细胞活化。结果与对照组相比,cuprizone模型组小鼠在Y迷宫试验中的自发性交替反应率减低(空间工作记忆能力下降),在旷场试验中的自发活动总路程延长(高活动性阳性症状);胼胝体部位髓鞘脱失,MBP表达减少;小胶质细胞和星形胶质细胞数量增多。ICA灌胃给药5周明显改善模型小鼠的空间工作记忆能力和高活动性阳性症状,减轻胼胝体部位髓鞘脱失,增高MBP的表达,抑制小胶质细胞和星形胶质细胞的活化。结论 ICA能够改善cuprizone模型小鼠的认知功能障碍和高活动性阳性症状,其机制与减轻脑白质髓鞘脱失和拮抗神经炎症有关,提示ICA具有治疗精神分裂症的潜能。

关键词: 淫羊藿苷, 精神分裂症, 双环己酮草酰二腙, 髓鞘脱失, 神经炎性反应

Abstract: Objective To investigate the effects of icariin (ICA) on the behavioral and pathological changes in the mice with cuprizone induced schizophrenia. Methods The model was established by feeding 0.2% cuprizone-containing fodder for 5 weeks in C57BL/6 mice. The behavioral changes were detected by open-field test and Y-maze test. The oil red O staining was applied to observe the demyelination, and the immunohistochemical method was used to detect the expression of myelin basic protein (MBP) and the number of microglia and astrocytes. Results Compared with the control group, the cuprizone model group showed a lower spontaneous alternation rate (decreased spatial working memory) in the Y-maze test and a longer total course of spontaneous activity (high activity positive symptom) in the open-field test. Moreover, the demyelination, decreased expression of MBP, and increased number of microglia and astrocyte were observed in the corpus callosum of model mice. Intragastric administration of ICA for 5 weeks significantly improved the spatial working memory impairment and the positive symptoms of high activity, reduced the demyelination, increased the expression of MBP, and inhibited the activation of microglia and astrocytes in the corpus callosum of cuprizone model mice. Conclusion ICA could improve the positive symptom and cognitive impairment in the mice with cuprizone-induced schizophrenia, and the mechanisms might be related to the inhibitory effects of ICA on the demyelination and neuroinflammation. These results suggested that ICA may have the potential to treat schizophrenia.

Key words: icariin, schizophrenia, cuprizone, demyelination, neuroinflammation

中图分类号:

R745.1

陈溪, 马登磊, 李林. 淫羊藿苷对cuprizone诱导精神分裂症样小鼠模型行为学变化、髓鞘脱失及神经炎性反应的影响[J]. 首都医科大学学报, 2021, 42(5): 761-767.

Chen Xi, Ma Denglei, Li Lin. Effects of icariin on the behavioral changes, demyelination and neuroinflammation in mice with cuprizone-induced schizophrenia[J]. Journal of Capital Medical University, 2021, 42(5): 761-767.

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淫羊藿苷对cuprizone诱导精神分裂症样小鼠模型行为学变化、髓鞘脱失及神经炎性反应的影响

Effects of icariin on the behavioral changes, demyelination and neuroinflammation in mice with cuprizone-induced schizophrenia

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