山茱萸多糖对衰老模型大鼠学习记忆能力及海马突触可塑性的影响

目的:观察山茱萸多糖对衰老模型大鼠学习记忆能力、海马脑源性神经生长因子(BDNF),酪氨酸蛋白激酶B(Trk B)蛋白表达及海马长时程增强(LTP)的影响,并探讨其机制。方法:清洁级SD大鼠40只,随机数字表法分为正常组、模型组、山茱萸多糖低、高剂量组,每组10只,采用D-半乳糖(140 mg·kg~(-1)·d-1)皮下注射构建大鼠衰老模型,同时正常组、模型组每天给予生理盐水、低剂量组和高剂量组给予山茱萸多糖(0.14,0.28 g·kg~(-1)·d-1)灌胃6周。Morris水迷宫检测学习记忆能力,高频刺激海马CA3区Schaffer侧支,在同侧海马CA1区诱导LTP的方法检测大鼠海马神经元突触可塑性的变化,免疫组化法检测海马神经元BDNF和Trk B蛋白的表达情况。结果:与正常组比较,模型组平均逃避潜伏期明显延长,在目标象限内游泳的距离占总距离的百分比和探索次数明显减少,海马LTP幅度显著降低,海马BDNF和Trk B蛋白表达降低(P0.01)。高剂量组与模型组比较平均逃避潜伏期明显降低,在目标象限内游泳的距离占总距离的百分比和探索次数明显升高,海马LTP幅度显著升高,海马BDNF和Trk B蛋白表达升高(P0.01)。结论:山茱萸多糖可通过提高海马BDNF和Trk B的表达及大鼠海马CA1区的LTP,明显改善突触的可塑性,这可能是山茱萸多糖提高学习记忆能力的重要机制之一。

Effects of Polysaccharide from Corni Fructus on Learning and Memory Ability and Hippocampal Synaptic Plasticity of Aging Model Rats

Objective: To investigate the effects of polysaccharide from Corni Fructus on learning and memory ability, protein expression levels of brain derived neurotrophic factor(BDNF) and tyrosine kinase B(TrkB) in hippocampus, and hippocampal long-term potentiation (LTP) of the aging model rats. Method: Totally 40 clean SD rats were randomly divided into normal group, model group, low dose group and high dose group by random number table, n=10 in each group. The models of aging rats were established by subcutaneously injecting D-galactose (140 mg·kg^-1·d^-1). The rats in normal group and model group received normal saline every day, while the rats in low dose group and high dose group were given with polysaccharide from Corni Fructus(0.14,0.28 g·kg^-1·d^-1, correspondingly) by intragastric administration for 6 weeks. The learning and memory ability of rats was tested by Morris Water Maze. The Schaffer collateral of hippocampal CA3 region was stimulated by high frequency stimulation (HFS), and LTP in CA1 region of the ipsilateral hippocampus was induced to detect the synaptic plasticity changes of hippocampal neurons in rats. The protein expression levels of BDNF and TrkB in hippocampal neurons were detected by immunohistochemistry. Result: As compared with the normal group, the average escape latency of model group was prolonged significantly, the percentage of swimming distance of the target quadrant in total distance and the frequency of exploration were decreased significantly, the protein expression levels of BDNF and TrkB in the hippocampus were reduced, and the extent of LTP in hippocampus was decreased significantly (P < 0.01). As compared with the model group, the average escape latency of high dose group was decreased significantly; the percentage of swimming distance of the target quadrant in total distance and the frequency of exploration were increased significantly, the protein expression levels of BDNF and TrkB in hippocampus were increased, and the extent of LTP in hippocampus was increased significantly (P < 0.01). Conclusion: Polysaccharides from Corni Fructus may significantly improve the synaptic plasticity in the aging model rats by increasing the protein expression levels of BDNF and TrkB in hippocampus and increasing LTP of hippocampal CA1 region; this may be one of its important mechanisms for improving the ability of learning and memory of the aging rats.