目的: 探究肉苁蓉总苷是否通过调控突触可塑性进而改善睡眠剥夺模型大鼠学习认知功能。方法: 50只雄性Wistar大鼠随机分为空白对照组(Control)、平台对照组(PC)、模型组(Model)、肉苁蓉总苷组(GCs)、艾司唑仑组(Est)。通过改良多平台水环境法制备大鼠睡眠剥夺模型,使用Morris水迷宫、旷场实验分别检测大鼠空间认知功能和情绪变化,尼氏染色观察大鼠海马CA1区神经细胞形态、数量的改变,Western blot和RT-PCR分别检测突触素(SYN)、突触后膜致密物质95(PSD-95)、脑源性神经营养因子(BDNF)的表达水平。结果: Morris水迷宫结果表明,与Control组比较,Model组大鼠学习认知能力明显下降(P＜0.05),GCs治疗后大鼠的学习记忆功能得到改善(P＜0.05);旷场实验结果显示,与Control组相比,Model组大鼠的运动路程和站立次数显著增加(P＜0.05),静止时间明显缩短(P＜0.05),焦虑情绪增加。给予GCs治疗后,运动路程和站立次数减少(P＜0.05),静止时间增加(P＜0.05),焦虑情绪得到改善。Western blot和RT-PCR结果表明,Model组大鼠BDNF、SYN和PSD-95蛋白和基因表达水平均明显下降(P＜0.05);给予GCs治疗后,可以显著上调BDNF、SYN和PSD-95的表达量(P＜0.05)。结论: 肉苁蓉总苷可能通过调控突触相关标志物的表达影响突触可塑性,进而改善睡眠剥夺模型大鼠学习认知功能。
Objective: To explore whether the glycosides of cistanche can improve the learning and cognitive function of sleep deprivation model rats by regulating synaptic plasticity. Methods: Fifty male Wistar rats were randomly divided into blank control group (Control), platform control group (PC), model group (Model), glycosides of cistanche group (GCs) and estazolam group (Est). The sleep deprivation model of rats was prepared by modified multi-platform water environment method. Morris water maze and open field test were used to detect the spatial cognitive function and emotional changes of rats. Nissl staining was used to observe the changes of morphology and quantity of nerve cells in hippocampal CA1 area of rats. Western blot and RT-PCR were used to detect the expression levels of synaptophysin (SYN), postsynaptic membrane dense substance 95 (PSD-95) and brain-derived neurotrophic factor (BDNF). Results: Morris water maze results showed that compared with the Control group, the learning and cognitive ability of rats in the Model group was significantly decreased (P＜0.05), and the learning and memory function of rats was improved after GCs treatment (P＜0.05). The results of the open field test showed that compared with the Control group, the movement distance and standing times of the Model group were significantly increased (P＜0.05), the resting time was significantly shortened(P＜0.05), and the anxiety was increased, while after GCs treatment, the movement distance and standing times decreased (P＜0.05), the resting time increased (P＜0.05), and the anxiety was improved. The results of Western blot and RT-PCR showed that the protein and gene expression levels of BDNF, SYN and PSD-95 in the Model group were significantly decreased (P＜0.05), while after treatment with GCs, the expression levels of BDNF, SYN and PSD-95 were significantly up-regulated (P＜0.05). Conclusion: Glycosides of cistanche may affect synaptic plasticity by regulating the expression of synaptic related markers, thereby improving the learning and cognitive function of sleep deprivation model rats.
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