目的:明确肉苁蓉总苷(GCs)改善快速老化小鼠(SAMP8)认知功能障碍是否特异性介导雄激素受体(androgen receptor, AR)调控突触相关蛋白的表达。方法:7月龄雄SAMP8小鼠78只随机分为模型组、GCs组、GCs+氟他胺(F)组、GCs+氟维司群(ICI)组、F组、ICI组。采用Morris水迷宫检测各组小鼠学习记忆功能;Western blot和RT-PCR检测各组小鼠海马突触素(synaptophysin, SYN)、突触后致密物(postsynaptic density-95, PSD-95)、脑源性神经营养因子(brain-derived neurotrophic factor, BDNF)的表达。结果:GCs可以明显改善SAMP8小鼠的学习认知功能,GCs+F组和GCs+ICI组小鼠的学习记忆功能较GCs组有明显降低;Western blot和RT-PCR显示,与模型组相比,GCs组BDNF、SYN、PSD-95在蛋白水平和基因水平的表达均显著增加(P＜0.05);与GCs组相比,GCs+F组、GCs+ICI组SYN表达增加,BDNF和PSD-95表达显著性下降(P＜0.05)。结论:GCs可能特异性介导AR提高SAMP8小鼠的突触可塑性,进而改善学习认知功能。
Objective: To clarify whether general cistanosides (GCs) ameliorates cognitive dysfunction in rapidly aging mice (SAMP8) by mediating specific androgen receptor (AR) in regulation of expression of synaptic protein. Methods: A total of 76 7-month-old male SAMP8 mice were randomly divided into the model group, GCs group, GCs + flutamide (F) group, GCs + fulvestrant (ICI) group, F group, and ICI group. The learning and memory functions of mice in each group were tested with Morris water maze. Western blotting and RT-PCR were used to test the expression level of synaptophysin (SYN), postsynaptic density-95 (PSD-95) and the brain-derived neurotrophic factor (BDNF) of mice in each group. Results: GCs significantly improved the learning and cognitive function of SAMP8 mice. Comparing with the GCs group, the learning and memory function of mice in the GCs+F group and GCs+ICI group was significantly lowered. Western blotting and RT-PCR results showed that the expression level of BDNF, SYN, and PSD-95 were significantly increased at the protein level and gene level in the GCs group compared with the Model group (P＜0.05). SYN expression level was increased in the GCs+F and GCs+ICI group, and expression levels of BDNF and PSD-95 were significantly decreased in the GCs+F and GCs+ICI group compared with the GCs group (P＜0.05). Conclusion: GCs may specifically mediate AR to enhance synaptic plasticity in SAMP8 mice, which in turn improve learning and cognitive function.
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