中国中医药信息杂志2025，Vol.32Issue(7)：25-33,9.DOI:10.19879/j.cnki.1005-5304.202501049
基于NLRP3/Caspase-1/GSDMD信号通路探讨温和汤治疗热性惊厥药效机制
Exploration on the Pharmacodynamic Mechanism of Wenhe Decoction in the Treatment of Febrile Seizures Based on the NLRP3/Caspase-1/GSDMD Signaling Pathway
摘要
Abstract
Objective To investigate the mechanism of Wenhe Decoction in the treatment of febrile seizures through network pharmacology based on NLRP3/Caspase-1/GSDMD signaling pathway;To conduct experimental verification.Methods The active components and targets of Wenhe Decoction were retrieved and screened through TCMSP,BATMAN-TCM,PubChem databases and SwissADME platform.The disease targets of febrile seizures were found in GenCards,OMIM and DisGeNET databases.The intersection targets of Wenhe Decoction and the disease and the active components corresponding to the intersection targets were imported into Cytoscape 3.7.2 software to construct the Chinese materia medica-active components-targets network.The intersection targets were submitted to the STRING database to construct a protein-protein interaction network,and then the intersection targets were imported into the Metascape database for GO and KEGG pathway enrichment analysis.The febrile seizures rat model was established,and Wenhe Decoction of 4.05,8.1 and 16.2 g/kg were given respectively by gavage for 21 days.The rats were placed in batches in(45±0.5)℃constant temperature water bath to induce convulsive seizures,and the convulsive latency time and convulsive duration of rats were recorded.The behavioral differences of mice were observed.The morphology of hippocampal tissue were observed by HE and Nissl staining.The ROS content of hippocampal tissue was detected by DHE fluorescent probe technology.The serum ATP,GABA,Glu,Caspase-1,GSDMD,IL-1β and IL-18 contents were detected by ELISA,and the expression of NLRP3 inflammasome-related protein in hippocampal tissue was detected by Western blot.Results Network pharmacology analysis obtained 98 active components of Wenhe Decoction and 1 838 targets.162 targets were obtained by intersecting with disease targets,the core components for the treatment of febrile seizures were β-sitosterol,quercetin,luteolin,trans-squalene,sitosterol,saponin,etc.,and the core targets were EGFR,TNF,JUN,MTOR,etc.,and mainly through the regulation of inflammatory response,apoptosis,mitochondrial function and energy metabolism,mediating anti-inflammatory pathways such as PI3K-Akt signaling pathway and calcium signaling pathway to exert anticonvulsant effects.The experimental results showed that Wenhe Decoction could prolong the convulsive latency and shorten the duration of convulsions in febrile seizures model rats,decrease the level of convulsions,and the pathological damage of hippocampal tissue was improved and damaged neurons were repaired.The serum contents of ROS,Glu,Caspase-1,GSDMD,IL-1β and IL-18 were significantly reduced,and ATP and GABA contents significantly increased.The protein expressions of NLRP3,ASC,pro-Caspase-1,pro-IL-1β and pro-IL-18 in hippocampal tissue significantly decreased.Conclusion Wenhe Decoction may intervene in febrile seizures rats through NLRP3/Caspase-1/GSDMD signaling pathway,inhibit pyroptosis to reduce the occurrence of neuroinflammation,and then affect the balance of neurotransmitters Glu and GABA to play a role in anti-febrile seizures and prevent brain tissue damage.关键词
热性惊厥/温和汤/网络药理学/实验验证/NLRP3/Caspase-1/GSDMD信号通路Key words
febrile seizures/Wenhe Decoction/network pharmacology/experimental verification/NLRP3/Caspase-1/GSDMD signaling pathway分类
医药卫生引用本文复制引用
余欢,郭文媛,邓羿駃,李鑫,王孟清,帅云飞..基于NLRP3/Caspase-1/GSDMD信号通路探讨温和汤治疗热性惊厥药效机制[J].中国中医药信息杂志,2025,32(7):25-33,9.基金项目
国家自然科学基金(82174437) （82174437）
湖南省自然科学基金(2025JJ80971) （2025JJ80971）
湖南省教育厅科学研究项目(19B425) （19B425）
湖南中医药大学中医儿科学湖南省"双一流"学科建设项目(4912-0005001010) （4912-0005001010）
