天麻素对阿尔茨海默病小鼠的脑内氧化应激及tau蛋白磷酸化的影响

张浩 边诗宇 高飞 王英滨

[摘要] 目的 研究天麻素對AD模型小鼠脑内氧化应激及tau蛋白磷酸化水平的影响。 方法 实验分为正常对照组、AD模型组（tau 转基因小鼠）和天麻素治疗组，治疗组小鼠选取tau转基因小鼠，隔日给予天麻素[5 mg/（kg·d）]灌胃处理3个月，对照组和模型组小鼠（tau转基因小鼠）则均给予生理盐水灌胃处理。通过分子生物学及形态学相关技术检测各组小鼠脑内p-tau202磷酸化水平及CHAT的表达;并考察氧化应激相关指标的变化。 结果 Western blot及免疫荧光结果显示，模型组小鼠脑内p-tau202的表达高于对照组小鼠，而天麻素治疗组小鼠脑内p-tau202的表达水平较模型组小鼠降低;氧化应激结果显示，天麻素干预处理后，小鼠脑内的MDA含量降低，SOD活性明显升高;Western blot结果显示，与模型组小鼠相比较，天麻素治疗组小鼠脑内CHAT表达水平降低。 结论 天麻素能够通过减少氧化应激进而降低AD模型小鼠脑内tau蛋白的磷酸化水平，最终起到对神经元的保护作用。

[关键词] 天麻素;阿尔茨海默病;tau蛋白磷酸化;氧化应激;保护作用

[中图分类号] R285          [文献标识码] A          [文章编号] 1673-9701（2020）17-0033-04

The effect of gastrodin on oxidative stress and tau protein phosphorylation in the brain of the mice with Alzheimer's disease

ZHANG Hao1   BIAN Shiyu2   GAO Fei1   WANG Yingbin1

1.Department of Neurosurgery，Division Ⅱ，Central Hospital Affiliated to Shenyang Medical College，Shenyang   110024，China;2.Biotechnology Major，China Medical University，Shenyang   110024，China

[Abstract] Objective To mainly study the effect of gastrodin on oxidative stress（OS） and tau protein phosphorylation in the brain of the AD model mice. Methods In the experiment，the subjects were divided into the normal control group，the AD model group（tau transgenic mice）and the gastrodin intervention group. Tau transgenic mice were selected into the intervention group， which received gastrodin[5 mg/（kg·d）] in the form of intragastric administration every other day for 3 m， while normal saline was administrated in intragastric form to the mice in the control group and the AD model group（tau transgenic mice）. The p-tau202 phosphorylation level and the expression of CHAT in the brain of each group of mice were detected by the relevant techniques of molecular biology and morphology， and the changes of OS related indexes were also investigated. Results Western blot and immunofluorescence results showed that the p-tau202 expression in the brain of tau transgenic mice was higher than that in the brain of the mice in the control group， while the p-tau202 expression level in the brain of the mice in the gastrodin intervention group was lower than that of tau transgenic mice. OS results showed that after gastrodin intervention， MDA content in the brain of the mice decreased and SOD activity significantly increased. Western blot results showed that compared with that of the mice in the AD model group，the CHAT expression level in the brain of the mice in the gastrodin intervention group decreased. Conclusion Gastrodin can reduce the phosphorylation level of tau protein in the brain of AD model mice by reducing OS，and ultimately play a protective role on neurons.

[Key words] Gastrodin; Alzheimer's disease（AD）; Tau protein phosphorylation; Oxidative stress（OS）; Protective role

阿尔茨海默病（Alzheimers disease，AD）是由德国学者Alois Alzheimer发现的一种中枢神经系统变性病，迄今为止已有100多年的研究历史[1-2]。如今，AD发病率逐年上升，并已成为世界上最常见的痴呆类型[3-4]。AD的主要病理特征主要体现在两方面：①大脑皮质、海马、杏仁核和丘脑中出现大量β-淀粉样蛋白（Amyloid-β，Aβ）沉积形成的老年斑（Senile plaque，SP）;②大脑皮质和海马存在大量由tau蛋白过度磷酸化进而形成的神经纤维缠结（Neurofibrillary tangles，NFTs）[5-7]。AD发病的确切原因尚不清楚，发病机制复杂，其病因与多种因素有关。……