时珍国医国药2026，Vol.37Issue(17)：3228-3237,10.DOI:10.70976/j.1008-0805.SZGYGY-2026-1705
上下两济丹调控NLRP3/Caspase-1/GSDMD通路改善AD小鼠学习记忆能力及神经损伤的机制研究
Mechanism study of Shangxia Liangji Pill(上下两济丹)in regulating the NLRP3/Caspase-1/GSDMD pathway to improve learning and memory ability and ameliorate neural injury in AD mice
摘要
Abstract
Objective To investigate the improving effects of Shangxia Liangji Pill(上 下 两 济 丹,SXLJP)on learning and memory ability and neuro injury in APP/PS1 mice,and clarify whether it acts by regulating the NLRP3/Caspase-1/GSDMD pathway.Methods APP/PS1 mice served as the Alzheimer's disease(AD)model and were assigned to the control group,model group,low/middle/high-dose SXLJP groups,and donepezil hydrochloride group.After administration,novel object recognition test and Morris water maze test were used to assess learning and memory;Nissl and Golgi staining were performed to observe hippocampal neuronal and synaptic structures;Thioflavin S staining detected Aβ deposition;immunofluorescence and Western blot(WB)were used to measure the expression of neuroinflammatory indicators and pathway proteins.Results Compared with the model group,each dose of SXLJP significantly increased the novel object recognition index(P＜0.05),shortened the escape latency and distance to the platform in the Morris water maze,and increased the target quadrant residence time and platform crossings(P＜0.05 or P＜0.01).Nissl staining showed increased neuronal density and improved structural integrity in the hippocampal CA3 region(P＜0.05 or P＜0.01);Golgi staining and WB confirmed enhanced dendritic spine density and expression of PSD95 and SYN proteins,thus amelio-rating synaptic damage(P＜0.05 or P＜0.01).Additionally,it reduced hippocampal Aβ deposition(P＜0.05 or P＜0.01),down-regulated Iba1,CD86,IL-1β and TNF-α expression(P＜0.05),inhibited NLRP3,Caspase-1 and GSDMD-N protein expression.Conclusion SXLJP could ameliorate learning and memory impairment,alleviates neuronal/synaptic damage and Aβ deposition in APP/PS1 mice,with its mechanism possibly involving inhibiting neuroinflammation and regulating the NLRP3/Caspase-1/GSDMD pathway.关键词
上下两济丹/NLRP3/Caspase-1/GSDMD通路/阿尔茨海默病/学习记忆/海马组织/神经炎症Key words
Shangxia Liangji Pill(上下两济丹)/NLRP3/Caspase-1/GSDMD pathway/Alzheimer's disease/Learning and memory/Hippocampal tissue/Neuroinflammation分类
医药卫生引用本文复制引用
程炜,杨硕,陆毅,汪颖,谭爱华..上下两济丹调控NLRP3/Caspase-1/GSDMD通路改善AD小鼠学习记忆能力及神经损伤的机制研究[J].时珍国医国药,2026,37(17):3228-3237,10.基金项目
国家自然科学基金(82405523) （82405523）
国家中医药管理局科技专项(GZY-KJS-2025-012) （GZY-KJS-2025-012）
湖北省自然科学基金黄冈联合基金重点项目(2025AFD318) （2025AFD318）
