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积,抑制快速老化小鼠神经元凋亡,从而改善认知障                            [ 6 ]  KAZUO K,TAKESHI S,ITARU K,et al. Dysregulation
        碍。本研究也发现,ICA处理后可下调精神分裂症大鼠                               of schizophrenia-related aquaporin 3 through disruption of
        脑组织中 Caspase-3 表达,升高 Bcl-2/Bax 比值。这提示                   paranode influences neuronal viability[J]. J Neurochem,
        ICA可能通过调节凋亡相关蛋白的表达,改善精神分裂                               2018,147(3):395-408.
        症症状。                                               [ 7 ]  GU S,CUI F,YIN J,et al. Altered mRNA expression levels
                                                                of autophagy- and apoptosis-related genes in the FOXO
            中枢神经系统中的胆碱能系统对机体认知功能有
                                                                pathway in schizophrenia patients treated with olanzap-
        重要的调节作用,Ach主要存在于胆碱能神经元囊泡中,
                                                                ine[J]. Neurosci Lett,2021,746(16):135669-135673.
        与机体认知记忆功能密切相关——当Ach水平降低时,
                                                           [ 8 ]  陈溪,谷洪顺,张兰,等.淫羊藿苷对MK-801 致精神分裂
        机体认知功能会出现明显损伤,空间记忆能力会明显下
                                                                症模型小鼠的影响[J].中国药理学与毒理学杂志,2016,
        降;同时,胆碱能系统中 Ach E 可水解 Ach,而 Ch AT 可
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        促进 Ach 的合成 。Wang 等 在脑卒中痴呆模型小鼠                      [ 9 ]  LI F,ZHANG Y,LU X,et al. Icariin improves the cogni-
                      [22]
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        中发现,ICA 可通过调节胆碱能系统来改善认知功能。                              tive function of APP/PS1 mice via suppressing endoplas-
        本研究也发现,与模型组比较,经 ICA 处理的大鼠脑组                             mic reticulum stress[J]. Life Sci,2019,234:116739.
        织中Ach、ChAT水平升高,AchE水平降低。这提示ICA                     [10]  李菲,蔡锐,刘波,等.淫羊藿苷调节海马BDNF通路减轻
        可调节胆碱能系统,改善模型大鼠认知功能损伤。                                  血管性痴呆大鼠的学习记忆障碍[J].中国新药与临床杂
            BDNF 是一类重要的神经营养因子,参与神经元的                            志,2020,39(8):489-493.
        生长分化再生、抗凋亡以及突触可塑性等过程;CREB是                         [11]  HILL X L,RICHERI A,MCGREGOR R,et al. Neuro-be-
        BDNF 上游转录因子,可诱导下游多种突触或记忆相关                              havioral effects after systemic administration of MK-801
        蛋白的表达,其表达及磷酸化水平的降低会抑制BDNF                               and disinhibition of the anterior thalamic nucleus in rats:
        表达;另外,BDNF 水平还可激活 ERK1/2,进而引起                           potential relevance in schizophrenia[J]. Brain Res,2019,
                                                                1718:176-185.
        CREB 的活化(即磷酸化),形成自我调节的正反馈
                                                           [12]  ZHOU D,LV D,WANG Z,et al. GLYX-13 ameliorates
          [24]
        环 。本研究结果显示,ICA 各剂量组大鼠脑组织中
                                                                schizophrenia-like phenotype induced by MK-801 in
        BDNF mRNA 和蛋白的表达水平、ERK 和 CREB mRNA
                                                                mice:role of hippocampal NR2B and DISC1[J]. Front
        的表达水平、ERK1/2和CREB的磷酸化水平均不同程度
                                                                Mol Neurosci,2018,11:121.
        地升高,这提示ICA改善精神分裂症模型大鼠认知功能
                                                           [13]  BYE C M,HONG N S,MORE K,et al. The effects of
        损 伤 ,可 能 与 促 进 BDNF/ERK/CREB 信 号 通 路 表 达                pool shape manipulations on rat spatial memory acquired
        有关。                                                     in the Morris water maze[J]. Learn Behav,2019,47(1):
            综上所述,淫羊藿苷可提高精神分裂症模型大鼠的                              29-37.
        认知功能水平,可能与抑制神经元凋亡、调节胆碱能系                           [14]  DANIELA S. Acute food deprivation separates motor-acti-
        统、促进BDNF/ERK/CREB信号通路表达有关。                              vating from anxiolytic effects of caffeine in a rat open
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        中国药房    2021年第32卷第7期                                               China Pharmacy 2021 Vol. 32 No. 7  ·817 ·
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