摘要： 目的 通过给予脑源性神经营养因子（BDNF）特异性受体酪氨酸激酶受体B（TrkB）激动剂7，8-二羟基黄酮（7，8-DHF）、经典瞬时受体电位通道蛋白3（TRPC3）激动剂二酰基甘油类似物（OAG）和抑制剂吡唑化合物（Pyr3），研究BDNF对阿尔茨海默病（AD）小鼠的神经保护作用以及BDNF与TRPC3的相互关系。方法 将费城癌症研究所小鼠随机分为对照组、AD组、AD+7，8-DHF组、AD+OAG组和AD+7，8-DHF+Pyr3组，每组16只。小鼠侧脑室注射β淀粉样蛋白（Aβ）1-42制备AD小鼠模型；Morris水迷宫实验评估小鼠的空间学习记忆能力；Western blotting检测海马突触相关蛋白（synapsin-Ⅰ、CaMKⅡ-α）和TRPC3蛋白的表达；ELISA检测海马Aβ1-42的沉积程度。结果 与AD组相比，AD+7，8-DHF组和AD+OAG组小鼠学习记忆能力增强，Aβ沉积减轻，synapsin-Ⅰ、CaMKⅡ-α和TRPC3蛋白的表达增加；与AD+7，8-DHF组相比，AD+7，8-DHF+Pyr3组上述指标变化趋势相反。结论 BDNF通过上调TRPC3蛋白表达减轻Aβ异常沉积，进而改善AD小鼠的神经突触和认知功能。

β淀粉样蛋白诱导的阿尔茨海默病小鼠模型中BDNF通过上调TRPC3发挥神经保护作用

李爽¹, 张丽艳¹, 李雪建¹, 周义¹, 金戈²

1. 沈阳医学院基础医学院 病理生理学教研室, 沈阳 110034;
2. 沈阳医学院基础医学院 药理学教研室, 沈阳 110034

收稿日期:2019-12-30出版日期:2020-12-30发布日期:2020-12-09
通讯作者:张丽艳E-mail:1580471013@qq.com
作者简介:李爽(1994-),女,硕士研究生.
基金资助:辽宁省自然科学基金（201602722，20170540874）；沈阳医学院科学研究基金（20171008）


关键词: 阿尔茨海默病, 经典瞬时受体电位通道蛋白3, 脑源性神经营养因子, β淀粉样蛋白
Abstract: Objective To study the neuroprotective effects of brain-derived neurotrophic factor (BDNF) in a mouse model of Alzheimer disease (AD) and the relationship between BDNF and canonical transient receptor potential channel 3 (TRPC3) through administration of tyrosine kinase receptor B agonist 7,8-dihydroxyflavone (7,8-DHF),TRPC3 agonist 1-oleoyl-2-acetyl-sn-glycerol (OAG),and TRPC3 inhibitor pyrazole compound (Pyr3). Methods Institute of Cancer Research mice were randomly divided into control,AD,AD + 7,8-DHF,AD + OAG,and AD + 7,8-DHF + Pyr3 groups (n=16 in each group). Amyloid β-protein (Aβ) 1-42 was injected into the lateral ventricle of mice to generate the AD mouse model. Morris water maze test was performed to evaluate spatial learning and memory abilities of mice. Western blotting was performed to detect the expression of synapse-related proteins (synapsin-Ⅰ and CaMKⅡ-α) and TRPC3 in the hippocampus. The deposition level of hippocampal Aβ1-42 was detected via ELISA. Results The mice in the AD + 7,8-DHF and AD + OAG groups showed greater learning and memory capabilities,less Aβ deposition,and higher expression of synapsin-Ⅰ,CaMKⅡ-α,and TRPC3 proteins than those in the AD group. Compared with the AD + 7,8-DHF group,the above-mentioned parameters in the AD + 7,8-DHF + Pyr3 group showed opposite trends. Conclusion BDNF reduces the abnormal deposition of Aβ by upregulating the expression of TRPC3 protein,thereby increasing the expression of synaptic proteins and improving cognitive function of AD mice.
Key words: Alzheimer disease, canonical transient receptor potential channel 3, brain-derived neurotrophic factor, amyloid β-protein
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