涤痰汤通过调节IKB/NF-κB通路和细胞凋亡抑制阿尔茨海默病小鼠Tau蛋白过度磷酸化
Ditan Decoction inhibits Tau protein Hyperphosphorylation in mice with Alzheimer's dis-ease by regulating IKB/NF-κb pathway and apoptosis
程美佳 1袁常斌 2鞠业涛 1刘勇明 1史宝瑞 2杨雅丽 2谢思梦 1杨关林 2闵冬雨1
作者信息
- 1. 辽宁中医药大学附属医院中医药实验中心,辽宁沈阳 110032
- 2. 辽宁中医药大学中医脏象理论及应用教育部重点实验室,辽宁沈阳 110847
- 折叠
摘要
目的 探讨涤痰汤是否可以改善阿尔茨海默病(Alzheimer's disease,AD)小鼠的认知缺陷,并明确其神经保护作用及相关机制.方法 D-gal联合AlCl3造模的昆明小鼠作为AD动物模型.连续灌胃3个月后进行Y迷宫和Morris水迷宫(MWM)测试.Western blot 检测海马组织中 IKB、NF-κB、p-IKB、p-NF-κB、Bcl-2、Bax 和 Caspase-3 蛋白的表达.同时测定海马组织Tau和p-Tau蛋白水平.结果 MWM和Y迷宫结果显示,涤痰汤显著提高了 AD小鼠的空间学习记忆能力.WB结果显示,涤痰汤可减少AD小鼠脑内过度磷酸化的Tau蛋白.此外,涤痰汤治疗后还抑制了 AD小鼠海马p-IKB/IKB和p-NF-κB/NF-κB蛋白的表达,提示涤痰汤减少神经元凋亡可能通过IKB/NF-κB通路介导.同时,涤痰汤通过降低AD小鼠海马组织中Bax、Caspase-3蛋白表达,增加Bcl-2表达,显著抑制AD小鼠神经元凋亡.结论 涤痰汤通过调节IKB/NF-κB介导的神经元细胞凋亡改善AD小鼠认知功能障碍.
Abstract
Objective The aim of this study was to determine whether Ditan Decoction could ameliorate the cognitive deficits in AD mice,and to evaluate its neuroprotective effects and related mechanisms.Methods D-gal combined with AlCl3 induced Kun-ming mice as AD animal model.Y-maze and Morris water maze were performed after 3 months.The expressions of IKB,NF-κB,p-IKB,p-NF-κB,Bcl-2,Bax and Caspase-3 proteins were detected by Western blot.The levels of Tau and phos-phorylated Tau protein in hippocampus were measured.Results MWM and Y Maze test showed that Ditan Decoction significantly improved the spatial learning and memory ability of AD mice.WB results showed that Ditan Decoction reduced Hyperphosphoryla-tion Tau protein in the brains of AD mice.In addition,Ditan Decoction also inhibited the expression of p-IKB/IKB and p-NF-κB/NF-κB protein in the hippocampus of AD mice,suggesting that Ditan Decoction could reduce neuronal apoptosis through IKB/NF-κB pathway.At the same time,Ditan Decoction significantly inhibited the neuronal apoptosis of AD mice by decreasing the expression of Bax and Caspase-3 and increasing the expression of Bcl-2.Conclusion Di Tantang ameliorates cognitive im-pairment in AD mice by regulating IKB/NF-κB mediated neuronal apoptosis.
关键词
阿尔兹海默病/学习记忆/神经元炎症/凋亡/涤痰汤/中药复方Key words
Alzheimer's disease/Learning memory/Neuronal inflammation/Apoptosis/Ditan Decoction/Chinese medicine formulae引用本文复制引用
基金项目
国家自然科学基金(82174114)
辽宁省沈阳市科技计划(20-205-4-008)
辽宁省沈阳市科技局公共卫生研发专项(22-321-32-14)
辽宁中医药大学附属医院育苗项目(YM202132)
辽宁省教育厅科研项目(LJKQZ20222370)
出版年
2024
NETL
NSTL
万方数据