中药益肾平肝方对脱髓鞘模型小鼠社会交互行为的影响及作用靶点

doi:10.3969/j.issn.1006-7795.2019.02.011

首都医科大学学报 ›› 2019, Vol. 40 ›› Issue (2): 209-213.doi: 10.3969/j.issn.1006-7795.2019.02.011

中药益肾平肝方对脱髓鞘模型小鼠社会交互行为的影响及作用靶点

吴燕, 孙作厘, 马超, 朱虹, 尹冬青, 贾竑晓

首都医科大学附属北京安定医院国家精神心理疾病临床医学研究中心精神疾病诊断与治疗北京市重点实验室, 北京 100088

收稿日期:2019-01-18 出版日期:2019-03-21 发布日期:2019-04-15
通讯作者: 贾竑晓 E-mail:jhxlj@ccmu.edu.cn
基金资助:
国家自然科学基金面上项目（81873398），首都卫生发展科研专项重点攻关项目（首发2018-1-2122），北京中医药科技发展资金项目（JJ2018-42）。

Effects of Yishenpingganfang, an empirical prescription on social interaction behavior in mice exposed to cuprizone and its possible action target

Wu Yan, Sun Zuoli, Ma Chao, Zhu Hong, Yin Dongqing, Jia Hongxiao

The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing 100088, China

Received:2019-01-18 Online:2019-03-21 Published:2019-04-15
Supported by:
This study was supported by National Natural Science Foundation of China(81873398),Capital Health Research and Development of Special Funding(2018-1-2122),Beijing Chinese Medicine Science and Technology Development Fund Projects(JJ2018-42).

摘要/Abstract

摘要： 目的观察中药益肾平肝方对精神分裂症的治疗效果以及探究其作用的潜在靶标。方法实验动物采用成年雄性C57BL/6小鼠，6周龄，实验分为3组，每组10只：对照组，cuprizone（CPZ）模型组和益肾平肝方（Yishenpingganfang，YSPGF）治疗组，实验共进行6周。社会交互实验以及组织采集在最后一次给予中药治疗24h后进行。采用社会交互实验以评价YSPGF对小鼠精神分裂症样行为的影响；采用髓鞘特异性免疫组化和Western blotting观察成熟少突胶质细胞及少突胶质细胞前体细胞的表达变化。结果 CPZ模型组小鼠于第3周出现明显体质量下降（P<0.05），YSPGF治疗组与CPZ模型组相比，体质量差异无统计学意义（P>0.05）；社会交互实验：Trial 1实验中：对照组小鼠围绕陌生小鼠1（Stranger 1）的时间明显大于围绕空杯子（Empty）的时间（P<0.001）。YSPGF组与对照组类似，围绕Stranger 1与Empty的时间差异有统计学意义（P<0.01）。但模型组小鼠围绕Stranger 1与Empty的时间之间差异无统计学意义（P>0.05）。Trial 2实验中：对照组小鼠对新加入的Stranger 2较之已经熟悉的Stranger 1更加感兴趣（P<0.001）第；成熟少突胶质细胞特异性抗体髓鞘碱性蛋白（myelin basic protein，MBP）免疫组织化学染色和Western blotting显示：CPZ模型组小鼠成熟胶质细胞/髓鞘在胼胝体有一定程度缺失，YSPGF组与CPZ模型组相比，髓鞘脱失有所好转。进一步实验显示：少突胶质细胞前体细胞血小板源生长因子受体α（platelet-derived growth factor receptor-alpha，PDGFR-α）在CPZ诱导脱髓鞘后有反应性增生。结论中药YSPGF可以改善CPZ诱导小鼠的社会退缩，改善少突胶质细胞/髓鞘结构的损害。

关键词: 精神分裂症, 益肾平肝方, 少突胶质细胞, 双环己酮草酰二腙, 社会交互

Abstract: Objective To explore the effect and potential target of Yishenpingganfang (YSPGF) in schizophrenia treatment. Methods Totally 30 Young adult male C57BL/6 mice (6 weeks old) were randomly divided into three groups:normal control, cuprizone (CPZ) model, and YSPGF group. This study lasts for 6 weeks. Then, social interaction tests and brain tissue collections were carried out 24h later after 2-week period of drug admission. Social interaction was used to evaluate schizophrenia-like symptoms in mice exposed to cuprizone and partly treated by YSPGF. The mature oligodendrocyte/myelin deficiency and immature oligodendrocyte changes were observed with histological staining. Results The body weight in the model group were obviously decreased in week 3 compared with the control group (P<0.05). Social interaction included two trials:In trial 1, control mice spent more time interacting with the stranger mouse than with the empty cage and familiar one (P<0.001) as well as YSPGF group (P<0.01).In trial 2, control mice preferred to be near the new stranger mouse than the familiar one (P<0.001). In contrast, CPZ mice showed no preference between the empty cage and the stranger mouse in both trials 1 and 2.The oligodendrocyte/myelin deficiency existed in callosum through using mature oligodendrocyte maker myelin basic protein (MBP). Furthermore, we used immature oligodendrocyte maker platelet-derived growth factor receptor-alpha (PDGFR-α) and found that in model group mice these immature oligodendrocyte increased after the demyelination stage. Conclusion YSPGF could improve CPZ-induced psychosis-like behaviors and reduce oligodendrocyte/myelin deficiency.

Key words: schizophrenia, Yishenpingganfang, oligodendrocyte, cuprizone, social interaction

中图分类号:

吴燕, 孙作厘, 马超, 朱虹, 尹冬青, 贾竑晓. 中药益肾平肝方对脱髓鞘模型小鼠社会交互行为的影响及作用靶点[J]. 首都医科大学学报, 2019, 40(2): 209-213.

Wu Yan, Sun Zuoli, Ma Chao, Zhu Hong, Yin Dongqing, Jia Hongxiao. Effects of Yishenpingganfang, an empirical prescription on social interaction behavior in mice exposed to cuprizone and its possible action target[J]. Journal of Capital Medical University, 2019, 40(2): 209-213.

参考文献

[1] Laruelle M. Schizophrenia:from dopaminergic to glutamatergic interventions[J]. Curr Opin Pharmacol, 2014, 14:97-102.
[2] Harrison P J, Weinberger D R. Schizophrenia genes, gene expression, and neuropathology:on the matter of their convergence[J]. Mol Psychiatry, 2005, 10(1):40-68; image 45.
[3] Rajarajan P, Borrman T, Liao W, et al. Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk[J]. Science, 2018,362(6420). Pii:eaat 4311.
[4] Insel T R. Rethinking schizophrenia[J]. Nature, 2010, 468(7321):187-193.
[5] Jia H X, Zhu H, Liu S. Yi Shen Pin Gan Fang -a Chinese Herb Formula is effective in treating the Ultra High Risk for Psychosis population[C]//McGorry P. Early Intervention In Psychiatry.Milan,Italy:Wiley,2016:227.
[6] Yao R Q, Zhang L, Wang W, et al. Cornel iridoid glycoside promotes neurogenesis and angiogenesis and improves neurological function after focal cerebral ischemia in rats[J]. Brain Res Bull, 2009, 79(1):69-76.
[7] Huang C, Lin F, Wang G, et al. Tetrahydroxystilbene glucoside produces neuroprotection against 6-OHDA-Induced dopamine neurotoxicity[J]. Oxid Med Cell Longev,2018,2018:7927568.
[8] Murakami M, Nagahama M, Abe Y, et al. Humanin affects object recognition and gliosis in short-term cuprizone-treated mice[J]. Neuropeptides, 2017,66:90-96.
[9] Wang H N, Liu G H, Zhang R G, et al. Quetiapine ameliorates schizophrenia-like behaviors and protects myelin integrity in cuprizone intoxicated mice:the involvement of notch signaling pathway[J]. Int J Neuropsychopharmacol, 2015, 19(2):pii:pyv088.
[10] Zhang H, Zhang Y, Xu H, et al. Olanzapine ameliorates neuropathological changes and increases IGF-1 expression in frontal cortex of C57BL/6 mice exposed to cuprizone[J]. Psychiatry Res, 2014, 216(3):438-445.
[11] Schoonover K E, Farmer C B, Cash A E, et al. Pathology of white matter integrity in three major white matter fasciculi:A postmortem study of schizophrenia and treatment status[J].Br J Pharmacol,2019, doi:10.1111/bph.14612.
[12] Hof P R, Haroutunian V, Friedrich V L, et al. Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia[J]. Biol Psychiatry, 2003, 53(12):1075-1085.
[13] Takahashi N, Sakurai T, Davis K L, et al. Linking oligodendrocyte and myelin dysfunction to neurocircuitry abnormalities in schizophrenia[J]. Prog Neurobiol, 2011, 93(1):13-24.
[14] Xuan Y, Yan G, Wu R, et al. The cuprizone-induced changes in (1)H-MRS metabolites and oxidative parameters in C57BL/6 mouse brain:effects of quetiapine[J]. Neurochem Int, 2015,90:185-192.
[15] Messori L, Casini A, Gabbiani C, et al. Unravelling the chemical nature of copper cuprizone[J]. Dalton Trans, 2007(21):2112-2114.
[16] Zatta P, Raso M, Zambenedetti P, et al. Copper and zinc dismetabolism in the mouse brain upon chronic cuprizone treatment[J]. Cell Mol Life Sci, 2005, 62(13):1502-1513.
[17] Baxi E G,DeBruin J,Jin J, et al. Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone-induced demyelination[J].Glia, 2017, 65(12):2087-2098.
[18] Ma D L, Wang N, Fan X T, et al. Protective effects of cornel iridoid glycoside in rats after traumatic brain injury[J].Neurochem Res, 2018, 43(4):959-971.
[19] Zhao L H, Ding Y X, Zhang L, et al. Cornel iridoid glycoside improves memory ability and promotes neuronal survival in fimbria-fornix transected rats[J].Eur J Pharmacol, 2010, 647(1-3):68-74.
[20] 李雪莲, 杨翠翠,张兰,等.山茱萸环烯醚萜苷对蛋白磷酸酶2A催化亚基C磷酸化的调节机制[J].首都医科大学学报,2016,37(6):777-783.

中药益肾平肝方对脱髓鞘模型小鼠社会交互行为的影响及作用靶点

Effects of Yishenpingganfang, an empirical prescription on social interaction behavior in mice exposed to cuprizone and its possible action target

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