N-乙酰半胱氨酸通过海马区Notch1/hes1通路改善丙戊酸孤独症模型鼠的学习和记忆能力

doi:10.13418/j.issn.1001-165x.2019.04.007

中国临床解剖学杂志 ›› 2019, Vol. 37 ›› Issue (4): 390-396.doi: 10.13418/j.issn.1001-165x.2019.04.007

N-乙酰半胱氨酸通过海马区Notch1/hes1通路改善丙戊酸孤独症模型鼠的学习和记忆能力

项哲，　张应花，　何雪玲，　王丽君，　崔卫刚

新乡医学院基础医学院, 新乡医学院河南省医用组织再生重点实验室, 新乡市分子神经病学重点实验室，河南新乡 453003

收稿日期:2018-12-29 出版日期:2019-07-25 发布日期:2019-08-01
通讯作者: 张应花，副教授，博士，E-mail：zyhflo2013@163.com
作者简介:项哲（1991-），在读硕士，主要从事神经发育障碍性疾病方面的研究，E-mail：309660682@qq.com
基金资助:
国家自然科学基金（81301174）；新乡医学院博士科研启动基金（No.2013BSQD005）；新乡医学院精神神经医学学科群支持计划（2016PN-KFKT-18）

N-acetylcysteine ameliorates learning and memory abilities via the Notch1/hes1 signaling pathway of the hippocampus in a valproic acid-induced rat model of autism

XIANG Zhe, ZHANG Ying-hua, HE Xue-ling, WANG Li-jun, CUI Wei-gang

College of Basic Medicine, Xinxiang Medical University; Key Laboratory for Medical Tissue Regeneration of Henan Province, Xinxiang Medical University; Key Laboratory for Molecular Neurology of Xinxiang, Xinxiang 453003, Henan Province, China

Received:2018-12-29 Online:2019-07-25 Published:2019-08-01

摘要/Abstract

摘要： 目的　探讨N-乙酰半胱氨酸（N-acetylcysteine，NAC）能否改善孤独症模型鼠的学习和记忆能力及其作用机制。方法　利用丙戊酸（valproic acid，VPA）建立孤独症模型，通过三箱实验鉴定造模成功，Western blotting技术检测模型鼠海马区Notch1/hes1通路信号分子Notch1、Notch1胞内活性结构域（Notch intracellular domain，NICD）、Hes1、Jagged1变化，免疫荧光技术检测该通路信号下游靶基因Hes1的表达；然后用NAC干预，检测模型鼠学习和记忆能力的变化及Notch1/hes1信号通路关键信号分子的改变。结果　与对照组相比，VPA组大鼠找到平台的时间增加，跨越平台的次数及在靶象限的时间均减少，同时Notch1、NICD、Hes1、Jagged1的蛋白表达水平增加；而NAC干预以后，与VPA组相比，VPA+NAC组大鼠找到平台的时间减少，跨越平台的次数及在靶象限的时间均增加，同时海马脑区NICD、Hes1的蛋白表达均下降。结论　NAC可以改善VPA孤独症模型鼠学习和记忆能力，其作用机制可能与降低Notch1/hes1信号通路的过度活化有关。

关键词: 孤独症, 　N-乙酰半胱氨酸, 　Notch1, 　丙戊酸, 　学习记忆能力

Abstract: Objective　To investigate the effects of N-acetylcysteine (NAC) on learning and memory abilities, as well as the molecular mechanisms underlying the therapeutic roles in a valproic acid (VPA)-induced rat model of autism.　Methods　After prenatal exposure to VPA, the three-chamber test was used to identify the autism modeling, the expression of the signaling molecules of the Notch1/hes1 signaling pathway Notch1, Notch intracellular domain (NICD), Jagged1 and Hes1 in the hippocampus (HC) of autistic rats was determined using Western blot, the expression of Hes1 was determined using the immunohistochemical technique. Then, the roles of NAC in learning and memory abilities and the Notch1/hes1 signaling pathway in the VPA-induced autism model were investigated.　Results　Compared with the control group, VPA increased the time spent in finding the platform, decreased the number of crossing platform and the time spent in the platform. However, compared with the VPA group, VPA+NAC group lowered the time spent in finding the platform, increased the number of crossing platform and the time spent in the platform. Simultaneously, the expression levels of NICD and Hes1 in VPA+NAC group decreased in the HC of autism model, and NAC ameliorated learning and memory abilities in the autism model rats.　Conclusion　The beneficial effects of NAC in ameliorating learning and memory abilities of autism model may be mediated by attenuating the Notch1/hes1 pathway activity.

Key words: Autism; , , N-acetylcysteine; , , Valproic acid; , , Notch1; , , Learning and memory abilities

中图分类号:

R363.1

项哲, 张应花, 何雪玲, 王丽君, 崔卫刚. N-乙酰半胱氨酸通过海马区Notch1/hes1通路改善丙戊酸孤独症模型鼠的学习和记忆能力[J]. 中国临床解剖学杂志, 2019, 37(4): 390-396.

XIANG Zhe, ZHANG Ying-hua, HE Xue-ling, WANG Li-jun, CUI Wei-gang. N-acetylcysteine ameliorates learning and memory abilities via the Notch1/hes1 signaling pathway of the hippocampus in a valproic acid-induced rat model of autism [J]. Chinese Journal of Clinical Anatomy, 2019, 37(4): 390-396.

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N-乙酰半胱氨酸通过海马区Notch1/hes1通路改善丙戊酸孤独症模型鼠的学习和记忆能力

N-acetylcysteine ameliorates learning and memory abilities via the Notch1/hes1 signaling pathway of the hippocampus in a valproic acid-induced rat model of autism

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