中国中医药信息杂志2026，Vol.33Issue(4)：24-32,9.DOI:10.19879/j.cnki.1005-5304.202511143
基于网络药理学和实验验证探讨涤痰汤治疗阿尔茨海默病作用机制
Study on the Mechanism of Ditan Decoction in Treating Alzheimer Disease Based on Network Pharmacology and Experimental Verification
摘要
Abstract
Objective To explore the mechanism of Ditan Decoction in the treatment of Alzheimer disease(AD)based on network pharmacology and animal experiments.Methods Active components and corresponding targets of Ditan Decoction were retrieved through the TCMSP databases;the targets of AD were searched through the OMIM and GeneCards databases,and protein-protein interaction network map was constructed through STRING online database.GO and KEGG enrichment analysis of key targets were carried out by using R language.AD model was established by injecting β-amyloid25-35 into bilateral hippocampus of rats.The rats were divided into sham-operation group,model group,donepezil group,Ditan Decoction low-and high-dosage groups,Ditan Decoction high-dosage+AMPK inhibitor group,and were intervened accordingly.The pathomorphological changes in the hippocampus were observed by HE staining.Transmission electron microscope was used to detect the ultrastructural observation of neurons and synapses in rat hippocampus.The content of inflammatory factors in hippocampus was detected by ELISA.The expressions of AMPK,p-AMPK,NLRP3,ASC,Caspase-1,GSDMD-N,GAP43,SYN,PSD95,BDNF proteins in the hippocampus were detected by Western blot.The mRNA expression of AMPK,NLRP3,ASC,Caspase-1,GSDMD-N,GAP43,SYN,PSD95 and BDNF were detected by RT-qPCR.Results A total of 129 active components of Ditan Decoction and 102 main targets for treating AD were screened,with the core targets including NLRP3,CASP1,GAP43,SYN1,GSDMD,IL1B,BDNF,TNF,CREB1 and APP.KEGG pathway enrichment analysis suggested that AMPK signaling pathway,NOD like receptor signaling pathway,cholinerqic synapse,AD and gluta-matergic synapse may play a core regulatory role.Animal experiments showed that Ditan Decoction could improve the learning and spatial memory abilities of model rats significantly(P<0.05,P<0.01),alleviate pathological morphology damage in hippocampal tissue,and improve the ultrastructure of neurons and synapses in hippocampus;decrease the contents of IL-1β,IL-18 and TNF-α in hippocampus(P<0.05,P<0.01),down-regulate the expressions of ASC,Caspase-1,GSDMD-N proteins and mRNA(P<0.05,P<0.01),and up-regulate the expressions of GAP43,SYN,PSD95,BDNF proteins and mRNA(P<0.05,P<0.01).Ditan Decoction could increase the phosphorylated level of AMPK,thus down-regulate the expression of NLRP3 protein and mRNA(P<0.05,P<0.01).However,the co-treatment of AMPK inhibitor partially reversed the effects of Ditan Decoction on pyroptosis and synaptic plasticity.Conclusion Ditan Decoction can improve synaptic plasticity in AD via inhibiting AMPK/NLRP3-mediated pyroptosis.关键词
涤痰汤/网络药理学/阿尔茨海默病/细胞焦亡/AMPK/NLRP3信号通路Key words
Ditan Decoction/network pharmacology/Alzheimer disease/pyroptosis/AMPK/NLRP3 signaling pathway分类
医药卫生引用本文复制引用
张运辉,杨昆,杨梦琳,李勇华,伍大华,刘霞,程妍..基于网络药理学和实验验证探讨涤痰汤治疗阿尔茨海默病作用机制[J].中国中医药信息杂志,2026,33(4):24-32,9.基金项目
国家自然科学基金(82374441) （82374441）
重庆三峡医药高等专科学校-校级重点项目(XJ2022000505) （XJ2022000505）
重庆市中医药传承创新团队-三峡库区道地药材保护与利用多学科交叉创新团队(CXTD202303) （CXTD202303）
重庆市中医药管理局针灸推拿智能装备重点实验室(2024年) （2024年）
重庆市中医药重点学科(中医基础理论)建设项目(渝中医[2021]16号) （中医基础理论）
重庆三峡医药高等专科学校呼吸和老年疾病中医药防治创新研究中心(2024年) （2024年）
重庆三峡医药高等专科学校中医药防治呼吸和老年病团队(TIG202302) （TIG202302）
