摘要： 目的 研究鼠尾草酸（CA）通过抑制阿尔茨海默病（AD）小鼠脑内免疫炎症反应，减少 β淀粉样蛋白（Aβ）沉积的机制。方法 将18只APP/PS1转基因小鼠（AD模型）分为对照组和CA组，每组9只。CA组小鼠给予CA（20 mg·kg^-1 ·d^-1），对照组给予相同体积的生理盐水。水迷宫实验检测小鼠的认知能力；免疫荧光染色检测Aβ和神经胶质细胞（星形胶质细胞和小胶质细胞）在小鼠脑内的共定位情况；ELISA检测炎性细胞因子、肿瘤坏死因子-α （TNF-α）、白细胞介素（IL）-6和IL-1β的含量；Western blotting检测IL-6、NLRP3、TNF-α、IL-1β和转录因子核因子 κB（NF-κB）的表达。结果 与对照组相比，CA组小鼠脑内Aβ沉积数量明显减少（P<0.05），星形胶质细胞和小胶质细胞的活化被抑制。CA干预处理后，小鼠脑内炎性细胞因子的表达明显降低，转录因子NF-κB的表达被抑制（P<0.05）。行为学结果提示，CA组小鼠学习记忆能力明显改善（P<0.05）。结论 CA可通过抑制APP/PS1转基因小鼠脑内免疫炎症反应，减少AD小鼠脑内Aβ沉积数量，最终改善AD小鼠的认知功能障碍。

鼠尾草酸通过抑制阿尔茨海默病小鼠脑内炎症反应减少β淀粉样蛋白沉积的机制

贺晓文, 边竞

中国医科大学附属第一医院药学部, 沈阳 110001

收稿日期:2022-12-02出版日期:2023-07-30发布日期:2023-07-08
通讯作者:边竞E-mail:bianjingmirror@163.com
作者简介:贺晓文(1987-),女,药师,本科.
基金资助:国家自然科学基金（81901099）


关键词: 鼠尾草酸, APP/PS1转基因小鼠, β淀粉样蛋白, 炎症, 核因子κB
Abstract: Objective To investigate the mechanism by which carnosic acid（CA）reduces the deposition of amyloid-β （Aβ）protein in the brains of mouse model of Alzheimer’s disease（AD）. Methods Eighteen APP/PS1 transgenic mice were divided into CA and control groups，with 9 mice in each group. Mice in the CA group were treated with CA（20 mg·kg^-1 ·d^-1）for 2 months，and those in the control group were treated with an equal volume of normal saline. A water maze experiment was used to detect the cognitive ability of the mice， and immunofluorescence was used to detect the localization of Aβ and glial cells in their brains. Enzyme-linked immunosorbent assay （ELISA）and Western blotting were used to detect changes in inflammatory cytokines including Nod-like receptor protein 3（NLRP3）， tumor necrosis factor-α （TNF-α），interleukin（IL）-6，and IL-1β. Results Compared to that in the control group，the amount of Aβ deposition in the CA group was significantly reduced（P<0.05），and the activation of glials cells was inhibited. The expressions of inflammatory cytokines were significantly decreased in the CA group（P<0.05），and that of nuclear factor-κB was inhibited（P<0.05）. The behavioral results indicated that the learning and memory abilities of mice in the CA group were significantly improved（P<0.05）. Conclusion CA can reduce the amount of Aβ deposition by inhibiting the inflammatory response in the brains of AD mice，ultimately improving their cognitive dysfunction.
Key words: carnosic acid, APP/PS1 transgenic mice, amyloid-β protein, inflammation, nuclear factor-κB
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