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-1βsignaling pathway

作　　者：王朋 董园莉[2] 孙维梁 金轶[4] 梅嵘[5] 赵保胜 李求兵[1] Wang Peng;Dong Yuanli;Sun Weiliang;Jin Yi;Mei Rong;Zhao Baosheng;Li Qiubing(The Second Department of Healthcare,China-Japan Friendship Hospital,Beijing 100029,China;Department of Traditional Chinese Medicine,Peking University People's Hospital,Beijing 100044,China;Clinical Medical Research Institute,China-Japan Friendship Hospital,Beijing 100029,China;Department of Neurology,China-Japan Friendship Hospital,Beijing 100029,China;Department of Pharmacy,China-Japan Friendship Hospital,Beijing 100029,China;Beijing Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[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

出　　处：《国际中医中药杂志》2024年第5期594-599,共6页International Journal of Traditional Chinese Medicine

基　　金：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)。

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(1 mg/kg)、生慧益智汤组(15.6 g/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-1βmRNA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-1βmRNA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。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 ofβAmyloid 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-1βmRNA.Western Blot was used to detect expression of NLRP3,Caspase-1and IL-1βprotein.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-αdecreased(P<0.05,P<0.01),and the mRNA and protein expressions of NLRP3,Caspase-1 and IL-1βdecreased(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-1βsignaling 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 

分 类 号：R285.5[医药卫生—中药学]