复方柴金解郁片通过调节食欲素A、褪黑素和乙酰胆碱含量改善突触可塑性发挥抗抑郁失眠作用

Compound Chaijin Jieyu Tablets ameliorating insomnia complicated with depression by improving synaptic plasticity via regulating orexin A, melatonin, and acetylcholine contents

    摘要
  • 摘要:
    目的探讨复方柴金解郁片（CCJJYT）对失眠并发抑郁症模型大鼠的疗效及作用机制。
    方法将72只SD大鼠随机分为8组，分别为对照组、慢性不可预测轻度应激（CUMS）组、睡眠剥夺（SD）组、慢性不可预测轻度应激合并睡眠剥夺（CUMS + SD）组、阳性药物（盐酸文拉法辛 + 地西泮）组、CCJJYT高剂量（CCJJYT˗2×）组、中剂量（CCJJYT˗1×）组、低剂量（CCJJYT˗0.5×）组，每组9只。通过体重、摄食量和行为测试蔗糖偏好试验（SPT）、旷场试验（OFT）、强迫游泳试验（FST)和戊巴比妥诱导睡眠试验（PST）来评价抑郁样行为。苏木精-伊红（HE）染色和Golgi-Cox染色分别观察病理组织和突触形态的变化。采用酶联免疫吸附法（ELISA）检测食欲素A和乙酰胆碱的含量。采用免疫组化和Western blot检测食欲素受体1（OXR1）、褪黑素受体1（MT1A）、褪黑素受体2（MT1B）、酰胆碱酯酶（AChE）和胆碱乙酰转移酶（ChAT）的蛋白表达。
    结果模型组大鼠出现明显的行为学改变以及海马树突棘分支长度和突触数量减少，同时造模成功后食欲素A和乙酰胆碱的含量增加（P < 0.05），海马和前额叶皮层OXR1、MT1A、MT1B、ChAT和AChE表达发生改变（P < 0.05）。CCJJYT可改善大鼠抑郁性失眠行为(P < 0.05)和突触可塑性，与阳性药物组疗效相似。CCJJYT可减少食欲素A和乙酰胆碱的含量（P < 0.05），降低海马和前额叶皮层中OXR1和ChAT的表达（ P < 0.05），提高MT1A、MT1B和AChE蛋白的表达(P < 0.05）。
    结论CCJJYT具有较好的抗抑郁和改善失眠的作用，其机制可能是通过调节大鼠海马和前额叶皮层的食欲素A、褪黑素和乙酰胆碱含量从而改善突触可塑性，进而发挥抗抑郁失眠作用。

     

    Abstract:
    ObjectiveTo investigate the efficacy and mechanism of action of Compound Chaijin Jieyu Tablets (复方柴金解郁片, CCJJYT) in rats with insomnia complicated with depression.
    MethodsSeventy-two Sprague-Dawley rats were randomly assigned into eight groups: the control, chronic unpredictable mild stress (CUMS), sleep deprivation (SD), CUMS + SD, positive drug (venlafaxine hydrochloride + diazepam), CCJJYT high-dose (CCJJYT˗2×), medium-dose (CCJJYT˗1×), and low-dose (CCJJYT˗0.5×) groups, with nine rats in each group. Depression-like behavior was evaluated by body weight, food intake, and behavioral tests such as the sucrose preference test (SPT), open field test (OFT), forced swimming test (FST), and pentobarbital-induced sleep test (PST). Hematoxylin-eosin (HE) staining and Golgi-Cox staining were used to observe changes in pathological tissue and synaptic morphology, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of orexin-A and acetylcholine. The expression levels of orexin receptor 1 (OXR1), melatonin receptor 1 (MT1A), melatonin receptor 2 (MT1B), acetylcholinesterase (AChE), and choline acetyltransferase (ChAT) were detected by immunohistochemistry and Western blot.
    ResultsIn the present study, rats in the model group showed significant behavioral changes as well as a reduction in hippocampal dendritic branch length and synaptic number, along with increasing the content of orexin A and acetylcholine (P< 0.05), and altered expression levels of OX1R, MT1A, MT1B, ChAT, and AChE in the hippocampus and prefrontal cortex after modeling (P < 0.05). CCJJYT can improve depressive insomnia behavior and synaptic plasticity of rats (P < 0.05), which is similar to that of the positive drug group. It can also decrease the content of orexin A and acetylcholine, and reduce the expression levels of OXR1 and ChAT in hippocampus and prefrontal cortex (P < 0.05), and increase the expression levels of MT1A, MT1B, and AChE proteins (P < 0.05).
    ConclusionCCJJYT has good antidepressant and insomnia effects, probably through the regu-lation of orexin-A, melatonin, and acetylcholine content in hippocampus and prefrontal cortex of rats, improving synaptic plasticity and thus exerting antidepressant and insomnia effects.

     

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