中药药理与临床2025，Vol.41Issue(3)：34-41,8.
通脉开窍丸治疗血管性痴呆的作用机制
Mechanism of Tongmai Kaiqiao(通脉开窍)Pills in Treatment of Vascular Dementia
摘要
Abstract
Objective:To investigate the molecular mechanism of Tongmai Kaiqiao(通脉开窍)Pills in the treatment of vascular dementia(VD)based on network pharmacology and experimental studies.Methods:Potential targets and signaling pathways for the treatment of VD with Tongmai Kaiqiao Pills were identified through network pharmacology analysis.Seventy-two rats were randomly divided into a normal control group,a model group,Tongmai Kaiqiao Pills groups(27.6,13.8,and 6.9 g/kg),and a donepezil hydrochloride group(0.45 mg/kg).The VD rat model was established using a modified 2-VO method.The water maze test was used to evaluate changes in learning and memory abili-ties in each group.HE staining and Nissl staining were used to observe pathological morphology and neuron counts in the hippocampus.Transmission electron microscopy was employed to observe hippocampal neuronal ultrastructure.Immunohistochemistry(IHC)and Western blot(WB)were used to detect the expression of core targets and pathways in the hippocampus.Results:Tongmai Kaiqiao Pills were found to contain 121 active ingredients and 124 potential targets.VD was associated with 2 506 targets,with 76 overlapping targets identified between the two.Key targets included Caspase-3(CASP3),epidermal growth factor receptor(EGFR),mitogen-activated protein kinase 8(MAPK8),and hypoxia-inducible factor 1α(HIF1A).GO functional enrichment analysis yielded 338 entries for biological processes,prima-rily involving positive regulation,negative regulation of the apoptotic process,and response to lipopolysaccharides.Molecular function analysis yielded 64 entries,mainly enriched in transcription factor activity,while cellular component analysis yielded 86 entries,primarily focusing on caspase complexes,macromolecular complexes,chromatin,and synapses.KEGG pathway enrichment analysis primarily involved lipid and ath-erosclerosis,cancer pathways,phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT)signaling pathway,TNF signaling pathway,and AGE-RAGE signaling pathway.Animal experiments showed that compared with the model group,the Tongmai Kaiqiao Pills groups at 27.6,13.8,and 6.9 g/kg,as well as the donepezil hydrochloride group at 0.45 mg/kg,significantly improved the learning and memory abilities of VD rats.The morphology of hippocampal neurons was noticeably restored,the neuron counts increased,and mitochondrial structure and func-tion improved.The positive expression of CASP3 protein in hippocampal tissue was significantly reduced(P<0.01),while the expression of PI3K,AKT,p-PI3K,and p-AKT was significantly up-regulated(P<0.05 or P<0.01).The therapeutic effect of Tongmai Kaiqiao Pills dem-onstrated a dose-dependent relationship within a certain range.Conclusion:This study preliminarily revealed a relationship between the active ingredients of Tongmai Kaiqiao Pills and key proteins involved in VD,and the therapeutic effect on VD was exerted through a comprehensive regulatory network involving multiple targets and pathways,with the mechanism likely related to the activation of the PI3K/AKT signaling pathway and the inhibition of apoptosis.关键词
通脉开窍丸/网络药理学/血管性痴呆/细胞凋亡/磷脂酰肌醇-3激酶/蛋白激酶Key words
Tongmai Kaiqiao(通脉开窍)Pills/Network pharmacology/Vascular dementia/Cell apoptosis/Phosphatidylinositol-3-kinase(PI3K)/Protein kinase B(AKT)引用本文复制引用
赵楠楠,李彦杰,秦合伟,朱博超,丁慧敏,刘娟,马璐瑶,牛丽..通脉开窍丸治疗血管性痴呆的作用机制[J].中药药理与临床,2025,41(3):34-41,8.基金项目
中原英才计划中原青年拔尖人才项目(豫组通[2021]44号) （豫组通[2021]44号）
张仲景传承与创新专项"专项课题(编号:GZY-KJS-2022-043-3)) （编号:GZY-KJS-2022-043-3）
河南省中医药拔尖人才培养项目专项课题(编号:2022ZYBJ15) （编号:2022ZYBJ15）
河南中医药大学研究生科研创新项目(编号:2022KYCX075) （编号:2022KYCX075）
河南中医药大学研究生科研创新项目(编号:2022KYCX074). （编号:2022KYCX074）
