芪苓益脑汤对阿尔茨海默病小鼠炎症小体NOD样受体蛋白3表达的影响

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摘要目的探讨芪苓益脑汤（QYD）对阿尔茨海默病（AD）小鼠小胶质细胞炎症小体NOD样受体蛋白3（NLRP3）表达的影响。方法雄性APP/PS1双转基因小鼠24只按照随机数字表法分成QYD实验组（18.330 g/kg）、多奈哌齐组（0.001 g/kg）、模型组，每组8只，同窝同性别小鼠8只为对照组。模型组与对照组给予生理盐水2 mL/次，灌胃治疗30 d。采用Morris水迷宫测试APP/PS1双转基因小鼠学习记忆能力，采用透射电子显微镜观察小鼠大脑皮质区小胶质细胞的变化，采用免疫组织化学和实时定量聚合酶链式反应（RT-qPCR）检测大脑皮质区小胶质细胞NLRP3、海马区β-淀粉样蛋白（Aβ）的表达。结果与模型组比较，QYD组、多奈哌齐组小鼠的学习记忆能力明显改善（均P ＜ 0.05）；与模型组比较，QYD组、多奈哌齐组透射电镜观察小鼠大脑皮质区小胶质细胞结构明显改善；与模型组比较，QYD组、多奈哌齐组小鼠大脑皮质区NLRP3和海马Aβ mRNA表达均明显降低（均P ＜ 0.05）。结论 QYD可通过降低AD小鼠大脑皮质区小胶质细胞NLRP3的表达，改善AD小鼠的学习记忆能力。

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	李洋1 费洪新2 张晓杰1
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关键词 ：芪苓益脑汤, 阿尔茨海默病小鼠, NOD样受体蛋白3

Abstract：Objective To investigate the effect of Qiling Yinao Decoction (QYD) on the expressions of nod-like receptor protein 3 (NLRP3) in inflammatory microglia of Alzheimer′s disease (AD) mice. Methods According to the random number table method, 24 male APP/PS1 dual-transgenic mice were divided into the QYD experimental group (18.330 g/kg), Donepezil group (0.001 g/kg) and model group, with 8 mice in each group. And 8 mice of the same litter and the same sex were divided into the control group. Model group and control group were given 2 mL/time of normal saline, and gavage treatment for 30 d. Morris water maze was used to test the learning and memory ability of APP/PS1 dual-transgenic mice. Transmission electron microscope was used to observe the changes of microglia cells in the cerebral cortex of mice. Immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of NLRP3 in microglia cells in cerebral cortex and β-amyloid (Aβ) in hippocampus. Results Compared with the model group, the ability of learning and memory in QYD group and Donepezil group was significantly improved (all P ＜ 0.05). Compared with the model group, the structure of microglia in cerebral cortex in QYD group and Donepezil group was significantly improved. Compared with the model group, the expression of NLRP3 in cerebral cortex and Aβ mRNA in hippocampus of QYD group and Donepezil group were significantly decreased (P ＜ 0.05). Conclusion QYD can improve the learning and memory ability of AD mice by reducing the expression of NLRP3 in microglia cells in the cerebral cortex of AD mice.

Key words： Qiling Yinao Decoction Alzheimer′s disease mice Nod-like receptor protein 3

基金资助:齐齐哈尔医学科学院科技成果转化基金项目（QMSI2017ZH-01）。

通讯作者: 张晓杰（1965-），女，博士，教授，博士生导师，主要从事阿尔茨海默病、抑郁症、肿瘤研究。费洪新（1978-），男，博士，副教授，主要从事阿尔茨海默病、抑郁症研究。

引用本文:

李洋1 费洪新2 张晓杰1,3. 芪苓益脑汤对阿尔茨海默病小鼠炎症小体NOD样受体蛋白3表达的影响[J]. 中国医药导报, 2019, 16(32): 14-17,26.
LI Yang1 FEI Hongxin2 ZHANG Xiaojie1,3. Effect of Qiling Yinao Decoction on the expression of nod-like receptor protein 3 in inflammasome of Alzheimer′s disease mice. 中国医药导报, 2019, 16(32): 14-17,26.

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