首页|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

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

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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。
Ditan Decoction inhibits Tau protein Hyperphosphorylation in mice with Alzheimer's dis-ease by regulating IKB/NF-κb pathway and apoptosis
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.

Alzheimer's diseaseLearning memoryNeuronal inflammationApoptosisDitan DecoctionChinese medicine formulae

程美佳、袁常斌、鞠业涛、刘勇明、史宝瑞、杨雅丽、谢思梦、杨关林、闵冬雨

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辽宁中医药大学附属医院中医药实验中心,辽宁沈阳 110032

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

阿尔兹海默病 学习记忆 神经元炎症 凋亡 涤痰汤 中药复方

国家自然科学基金辽宁省沈阳市科技计划辽宁省沈阳市科技局公共卫生研发专项辽宁中医药大学附属医院育苗项目辽宁省教育厅科研项目

8217411420-205-4-00822-321-32-14YM202132LJKQZ20222370

2024

10.3969/j.issn.1008-0805.2024.02.04

时珍国医国药
时珍国医国药杂志社

时珍国医国药

北大核心
影响因子：0.887
ISSN：1008-0805
年,卷(期)：2024.35(2)
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