中国中西医结合急救杂志2025，Vol.32Issue(3)：298-305,8.DOI:10.3969/j.issn.1008-9691.2025.03.008
基于TNF-α/NF-κB信号通路联合网络药理学探讨安宫牛黄丸对自发性脑出血大鼠神经功能影响的作用机制
Investigating the mechanism of action of Angong Niuhuang pill on neurological function in rats with spontaneous intracerebral hemorrhage based on TNF-α/NF-κB signaling pathway
摘要
Abstract
Objective To explore the mechanism of Angong Niuhuang pill on the neurological function of rats with spontaneous intracerebral hemorrhage based on the tumor necrosis factor-α/nuclear factor-κB(TNF-α/NF-κB)signaling pathway combined with network pharmacology.Methods The targets for treatment of intracerebral hemorrhage with Angong Niuhuang pill were obtained using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),High-Throughput Experiment and Refeence-guided Database of Traditional Chinese Medicine(HERB).Key targets were screened for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and molecular docking.Then,rats were randomly divided into normal control group,model group,Angong Niuhuang pill group(administered by gavage at 270 mg·kg-1·d-1),and the Western medicine group(intraperitoneal injection of 4 500 mg·kg-1·d-1+furosemide 1.8 mg·kg-1·d-1),the dosage administered was the equivalent dose ratio calculated based on the body surface area for humans and animals.The intracerebral hemorrhage model was replicated by the autologous heart blood caudate nucleus injection method.After modeling,the neurological function behavior scores,brain tissue water content,pathological changes of brain tissue,blood-brain barrier permeability,and protein expression levels of NF-κB p65,tumor necrosis factor receptor 1(TNFR1),inhibitor NF-κBα(IκBα)and TNF-α in brain tissue of each group were observed.Results A total of 216 intersection genes were selected.The results of GO enrichment analysis and KEGG pathway annotation analysis predicted that the TNF-α/NF-κB inflammatory signaling pathway was one of the main regulatory pathways.The animal experiment results showed that at 72 hours after modeling,compared with the model group,the neurological function score,brain tissue water content,and blood-brain barrier permeability index evans blue(EB)content of the Angong Niuhuang pill group were significantly decreased[neurological function score:1.62±0.62 vs.2.23±0.58,brain water content:(77.7±0.49)%vs.(79.9±0.04)%,EB content(μg/L):490.50±100.79 vs.1 966.20±94.81,all P<0.05];the pathological observation of brain tissue showed that Angong Niuhuang pill could reduce the pathological damage of brain tissue around the hematoma,repair the blood-brain barrier,and alleviate brain edema;the Western blotting results showed that Angong Niuhuang pill could inhibit the protein expression of TNF-α,TNFR1,and NF-κB p65 in brain tissue[NF-κB p65 protein expresion(NF-κB p65/β-actin):2.27±0.52 vs.5.40±0.26;TNFR1 protein expression(TNFR1/β-actin):1.49±0.33 vs.2.52±0.04,TNF-α protein expression(TNF-α/β-actin):1.40±0.13 vs.2.29±0.18,all P<0.05],promote the protein expression of IκB-α(IκB-α/β-actin):0.78±0.02 vs.0.32±0.00,P<0.05).Conclusion Angong Niuhuang pill may regulate the TNF-α/NF-κB signaling pathway by inhibiting the expression of TNFR1 and promoting the expression of IκB-α,exerting neuroprotective effects.关键词
安宫牛黄丸/脑出血/网络药理学/肿瘤坏死因子-α/核转录因子-κB/核转录因子-κB抑制因子-α/肿瘤坏死因子受体 1Key words
Angong Niuhuang pill/Intracerebral hemorrhage/Network pharmacology/Tumor necrosis factor-α/Nuclear factor-κB/Inhibitor nuclear factor-κBα/Tumor necrosis factor receptor 1引用本文复制引用
吴敬强,范文俊,曹勇,谢磊,杜康,邰伦伟,郑慧军..基于TNF-α/NF-κB信号通路联合网络药理学探讨安宫牛黄丸对自发性脑出血大鼠神经功能影响的作用机制[J].中国中西医结合急救杂志,2025,32(3):298-305,8.基金项目
河南省中医药科研专项(2024ZY2090) Special Project of Traditional Chinese Medicine Scientific Research in Henan Province(2024ZY2090) （2024ZY2090）
