黄连解毒汤调控SYK信号通路改善APP/PS1小鼠学习记忆能力的机制探讨  

Exploring the mechanism of Huanglian Jiedu Decoction(黄连解毒汤)in ameliorating learning and memory ability of APP/PS1 mice through regulating the SYK signaling pathway

作　　者：周家琪 黄子轩 游秋云 谭爱华[2,3] ZHOU Jia-qi;HUANG Zi-xuan;YOU Qiu-yun;TAN Ai-hua(School of Pharmacy,Hubei University of Chinese Medicine,Wuhan 430065,China;Central Laboratory of Huanggang Hospital of Traditional Chinese Medicine Afiliated to Hubei University of Chinese Medicine,Huanggang 438000,China;Key Laboratory of Germplasm Improvement and Utilization of Medicinal Materials of Dabieshan Mountain,Huanggang Normal University,Huanggang 438000,China)

机构地区：[1]湖北中医药大学药学院,湖北武汉430061 [2]湖北中医药大学附属黄冈中医医院中心实验室,湖北黄冈438000 [3]黄冈师范学院大别山道地药材种质改良与利用湖北省重点实验室,湖北黄冈438000

出　　处：《时珍国医国药》2025年第6期1056-1064,共9页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金青年基金(82405523);湖北省中医药管理局中医药科研项目(ZY2023Q025);黄冈市卫生健康委黄冈市科技局中医药科研项目(黄卫发[2024]17号)。

摘　　要：目的探讨黄连解毒汤通过调控SYK信号通路对阿尔茨海默病(AD)模型APP/PS1小鼠认知功能的/改善作用及其潜在机制。方法6月龄APP/PS1小鼠随机分为模型组、HLJDD组、多奈哌齐组和小檗碱组,同月龄C57BL/6J小鼠为对照组。连续相应处理60天后,采用Morris水迷宫(MWM)和新物体识别实验(NOR)评估学习记忆能力;采用高尔基染色和刚果红染色分别检测突触可塑性和Aβ斑块沉积。RT-qPCR和Western blot检测APP及其切割相关蛋白(ADAM10、BACE1、PS1)、炎症因子(TNF-α、IL-10)及SYK/PI3K/Akt/GSK3β信号通路的表达。结果行为学结果显示,给药组相比模型组表现出更短的逃避潜伏期,增加的目标象限停留时间和穿越平台次数,表明学习和记忆能力增强;高尔基染色显示突触可塑性增强,刚果红染色显示Aβ斑块沉积减少。RT-qPCR和Western blot显示,给药组增加ADAM10表达,促进APP非淀粉样途径裂解,降低Aβ水平,上调抗炎因子IL-10,下调促炎因子TNF-α,缓解神经炎症。同时HLJDD显著增加SYK、PI3K、Akt、GSK3β磷酸化水平。结论黄连解毒汤可通过干预SYK/PI3K/Akt信号通路减少Aβ沉积,抑制神经炎症,增强突触可塑性,从而改善APP/PS1小鼠认知功能。Objective To investigate the ameliorating effect of Huanglian Jiedu Decoction(黄连解毒,HLJDD)on the cognitive function of APP/PS1 mice with Alzheimer's disease(AD)model by modulating the SYK signaling pathway and its potential mechanisms.Methods Six-month APP/PS1 mice were randomly divided into the model group,HLJDD group,donepezil group and berberine group,with age-matched C57BL/6J mice serving as the control group.After 60 days of administration,Morris Water Maze(MWM)and Novel Object Recognition(NOR)were used to evaluate the learning and memory ability of mice.Golgi staining and Congo red staining were employed to detect synaptic plasticity and Aβplaque deposition respectively.RT-qPCR and Western blot(WB)were used to measure the expression of APP and its cleavage-related proteins(ADAM10,BACE1,PS1),inflammatory factors(TNF-α,IL-10)and SYK/PI3K/Akt/GSK3βsignaling pathway.Results Behavioral results revealed that compared with the model group,the administration group exhibited shorter escape latency,increased target quadrant dwell time and more platform crossings,indicating enhanced ability of learning and memory.Golgi staining demonstrated improved synaptic plasticity,while Congo red staining showed reduced Aβplaque deposition.RT-qPCR and WB indicated the expression of ADAM10 in administration group was increased,with promoted non-amyloidogenic APP cleavage,reduced Aβlevels,up-regulated anti-inflammatory factor IL-10,down-regulated pro-inflammatory factor TNF-α,and alleviated neuroinflammation.Meanwhile,HLJDD significantly increased the phosphorylation levels of SYK,PI3K,Akt and GSK3β.Conclusion HLJDD can improve the cognitive function of APP/PS1 mice by intervening the SYK/PI3K/Akt signaling pathway to reduce Aβdeposition,inhibit neuroinflammation,and strengthen synaptic plasticity.

关 键 词：阿尔茨海默病 黄连解毒汤 脾酪氨酸激酶信号通路 APP/PS1小鼠 神经保护 

分 类 号：R285.5[医药卫生—中药学]