基于NLRP3/Caspase-1/IL-1β通路探讨生慧益智汤改善SAMP8小鼠学习记忆能力的作用机制
Exploration on mechanism of Shenghui Yizhi Decoction in improving learning and memory ability of SAMP8 mice based on NLRP3/Caspase-1/IL-1β signaling pathway
王朋 1董园莉 2孙维梁 3金轶 4梅嵘 5赵保胜 6李求兵1
作者信息
- 1. 中日友好医院保健部二部,北京 100029
- 2. 北京大学人民医院中医科,北京 100044
- 3. 中日友好医院临床医学研究所,北京 100029
- 4. 中日友好医院神经科,北京 100029
- 5. 中日友好医院药学部,北京 100029
- 6. 北京中医药大学北京中医药研究院,北京 100029
- 折叠
摘要
目的 观察生慧益智汤对AD模型快速老化小鼠(SAMP8)学习记忆能力的影响,并探讨其作用机制.方法 将24只SAMP8小鼠按随机数字表法分为模型组、安理申组(1mg/kg)、生慧益智汤组(15.6g/kg),每组8只,8只同龄、同品系的对抗快速老化小鼠(SAMR1)设为对照组,分别给予相应药物或等体积蒸馏水连续灌胃90 d.给药结束后,采用Morris水迷宫检测小鼠学习记忆和空间探索能力,免疫组化染色检测小鼠海马β淀粉样蛋白1-42(Aβ1-42)表达,ELISA法检测海马IL-1β、IL-6、TNF-α水平,采用实时荧光定量PCR、Western blot法检测海马组织核苷酸结合寡聚化结构域样受体3(NLRP3)、Caspase-1、IL-1β mRNA和蛋白表达.结果 与模型组比较,生慧益智汤组和安理申组小鼠空间探索能力和记忆能力改善(P＜0.05或P＜0.01),海马区Aβ1-42表达减少(P＜0.01),TNF-α、IL-6、IL-1β 水平降低(P＜0.01 或 P＜0.05),NLRP3、Caspase-1 及 IL-1β mRNA 及蛋白表达降低(P＜0.01或P＜0.05).结论 生慧益智汤可有效改善SAMP8小鼠的学习记忆能力,其机制可能与调控NLRP3/Caspase-1/IL-1β通路抑制炎症小体活化、抑制神经炎症反应有关.
Abstract
Objective To investigate the effects of Shenghui Yizhi Decoction on learning and memory ability of SAMP8 mice;To explore its mechanism.Methods Totally 24 male SAMP8 mice were randomly divided into model group,donepezil hydrochloride group(1 mg/kg)and Shenghui Yizhi Decoction group(15.6 g/kg),with 8 mice in each group,and eight anti rapid aging mice(SAMR1)of the same age and strain were set as the control group.The mice in each group were given corresponding medication or the same volume of distilled water for 90 days.After administration,Morris water maze was used to detect the learning and memory ability and space exploration ability of mice.Immunohistochemistry was used to detect expression of β Amyloid protein 1-42(Aβ1-42)in hippocampal.ELISA was used to detect the levels of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α).Real time PCR was used to detect expressions of NOD-like receptor thermal protein domain associated protein 3(NLRP3),cysteine protease-1(Caspase-1),and IL-1β mRNA.Western Blot was used to detect expression of NLRP3,Caspase-1and IL-1β protein.Results Compared with model group,the spatial exploration ability and memory ability of mice in Shenghui Yizhi Decoction group and donepezil hydrochloride group were improved(P＜0.05,P＜0.01),the expression of Aβ1.42 in hippocampus decreased(P＜0.05,P＜0.01),the contents of IL-1β,IL-6 and TNF-α decreased(P＜0.05,P＜0.01),and the mRNA and protein expressions of NLRP3,Caspase-1 and IL-1β decreased(P＜0.05,P＜0.01).Conclusion Shenghui Yizhi Decoction can effectively improve the learning and memory ability of SAMP8 mice,and its mechanism may be related to inhibiting the activation of inflammasome and neuroinflammatory response by regulating the NLRP3/Caspase-1/IL-1 β signaling pathway.
关键词
阿尔茨海默病/生慧益智汤/NLRP3炎症小体/神经炎症/交通心肾/小鼠Key words
Alzheimer disease/Shenghui Yizhi Decoction/NLRP3 inflammasome/Neuroinflammation/Coordinating heart and kidney/Mice引用本文复制引用
基金项目
国家自然科学基金(81503519)
中日友好医院青年课题(2020-1-QN-8)
中日友好医院临床研究与转化跃升项目(2022-NHLHCRF-LX-02-0123)
出版年
2024
NETL
NSTL
万方数据