基于Wnt/β-catenin信号通路探讨麝香对AD模型大鼠的影响及潜在机制  

To investigate the effect of musk on AD model rats and its potential mechanism based on Wnt/β-catenin signaling pathway

作　　者：秦涛 邓婷 徐颖[1] 孙涛[1] QIN Tao;DENG Ting;XU Ying;SUN Tao(School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Sichuan Chengdu 611137,China;Jintang Second People's Hospital,Sichuan Chengdu 610404,China)

机构地区：[1]成都中医药大学药学院,四川成都611137 [2]金堂县第二人民医院,四川成都610404

出　　处：《中药与临床》2025年第1期29-35,45,共8页Pharmacy and Clinics of Chinese Materia Medica

基　　金：四川省中医药管理局科学技术研究专项课题(2024MS594);成都中医药大学“杏林学者”学科人才科研提升计划(ZRQN2020008,MPRC2021034,MPRC2023011)。

摘　　要：目的:研究麝香对Aβ25-35诱导的阿尔茨海默病(Alzheimer disease,AD)模型大鼠的神经保护作用及潜在机制。方法:大鼠双侧海马内注射Aβ25-35寡聚体构建AD模型,随机分组后进行药物干预;采用Morris水迷宫评价麝香对AD模型大鼠的学习和记忆能力的影响;通过HE染色、尼氏染色检测大鼠的病理变化,Western blot(WB)、免疫组化、Elisa方法检测相关蛋白表达以及炎症因子(IL-1β、IL-6和TNF-α)水平,综合考察麝香对AD模型大鼠的治疗作用和潜在机制。结果:与模型组比较,麝香200 mg·kg^(-1)组大鼠逃逸潜伏期缩短,目标象限停留时间增加,目标象限穿越次数增多;麝香200 mg·kg^(-1)组大鼠海马组织中GSK-3β(Ser9)、PP2A和β-catenin蛋白表达显著增加,大脑皮层中炎症标志物(IL-1β、IL-6和TNF-α)表达明显降低。结论:麝香可能通过激活Wnt/β-catenin信号通路和减少炎症来缓解AD模型大鼠的记忆和学习障碍。Objective:To study the neuroprotective effect of musk on Aβ25-35-induced Alzheimer disease(AD)model rats and potential mechanism.Methods:The AD model was established by injecting Aβ25-35 oligomers into the hippocampus of rats,and drug intervention was performed after randomization.Morris water maze was used to evaluate the effects of musk on learning and memory ability of rats.The pathological alterations in rats were detected by H&E staining and Nissl staining techniques.The protein expression and levels of inflammatory factors(IL-1β,IL-6 and TNF-α)were assessed by Western blot(WB),immunohistochemistry and Elisa to investigate the therapeutic effect and potential mechanism of musk on AD model rats.Results:Compared with model group,the escape latency of rats in Musk 200 mg·kg^(-1) group was shortened with increased residence time in target quadrant and increased number of crossing times in target quadrant.The expressions of GSK-3β(Ser9),PP2A andβ-catenin protein in the hippocampus of rats in the musk 200 mg·kg^(-1) group were significantly increased,and the levels of inflammatory markers(IL-1β,IL-6 and TNF-α)in the cerebral cortex was significantly decreased.Conclusion:Musk may alleviate memory and learning impairment in AD model rats by activating Wnt/β-catenin signaling pathway and reducing inflammation.

关 键 词：麝香 阿尔茨海默病 AΒ25-35 WNT/Β-CATENIN 神经炎症 

分 类 号：R285.5[医药卫生—中药学]