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目的:观察安神定志方对阿尔茨海默病大鼠模型海马区tau蛋白磷酸化水平的影响及其相关机制。方法:SD大鼠随机分为正常组、模型组、安神定志方(低、中、高剂量组)和多哌齐特组,除正常组外其余组通过链脲佐菌素侧脑室注射复制阿尔茨海默病大鼠模型后给予相应药物灌胃治疗2周。通过Morris水迷宫试验检测大鼠学习记忆能力,HE染色检测海马区组织学形态,Western-blot检测脑组织海马组织tau蛋白磷酸化水平及BDNF和TrkB蛋白的表达丰度。结果:与空白组相比,模型组大鼠逃避潜伏期显著增加,跨越平台次数及有效停留时间明显减少,tau蛋白的磷酸化水平均明显升高,BDNF蛋白及TrkB蛋白磷酸化的表达水平明显降低,差异具有统计学意义(P<0.05)。与模型组相比,安神定志方各剂量组均能明显降低AD大鼠逃避潜伏期,增加跨越平台次数及有效停留时间,抑制tau蛋白的磷酸化水平均,上调BDNF蛋白及TrkB蛋白磷酸化的表达水平,差异具有统计学意义(P<0.05)。结论:安神定志方能够通过激活BDNF/TrkB信号通路抑制tau蛋白的磷酸化,促进AD大鼠学习、记忆能力。
Abstract：Objective: To observe the effect of AnshenDingzhiDecoction on tau phosphorylation in hippocampus of Alzheimer's disease rat model and its related mechanism. Methods: SD rats were randomly divided into the control group, the model group, AnshenDingzhiDecoction(low, medium and high dose group) and the Dopazide group. Except for the control group, the rats in the other groups were injected with streptozotocin into the lateral ventricle to replicate the model of Alzheimer's disease and then given corresponding drugs for 2 weeks. Orris water maze test was used to detect learning and memory ability of rats, HE staining was used to detect hippocampal histological morphology, and western-blot was used to detect tau phosphorylation level and expression abundance of BDNF and TrkB protein in hippocampal tissue of rats. Results:The escape latency of the model group was significantly increased, the number of crossing platforms and effective residence time were significantly reduced, the phosphorylation level of tau protein was significantly increased, and the phosphorylation levels of BDNF and TrkB protein were significantly decreased when compared with the control group, the difference has statistically significant(P<0.05). AnshenDingzhi Fang could significantly reduce the escape latency of AD rats, increase the number of crossing platforms and effective residence time, inhibit the phosphorylation of tau protein, and up-regulate the phosphorylation of BDNF and TrkB protein, the difference was statistically significant when compared with the model group(P<0.05). Conclusion:AnshenDingzhi Fang can inhibit the phosphorylation of tau protein by activating BDNF/TrkB signaling pathway and promote the learning and memory ability of AD rats.
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基本信息:
DOI：10.13210/j.cnki.jhmu.20191010.002
中图分类号:R285.5
引用信息:
[1]王欣波,赵宇.安神定志方对阿尔茨海默病大鼠Tau蛋白磷酸化及BDNF/TrkB信号通路的影响[J].海南医学院学报,2019,25(21):1612-1616.DOI:10.13210/j.cnki.jhmu.20191010.002.
基金信息:
黑龙江省自然科学基金面上项目(H2018063)~~
2019-10-10
2019-10-10
2019-10-10