国际神经病学神经外科学杂志2025,Vol.52Issue(3):1-9,9.DOI:10.16636/j.cnki.jinn.1673-2642.2025.03.001
天麻钩藤饮加减对脑出血小鼠的神经保护作用及其对高迁移率组蛋白B1/Toll样受体4信号通路的影响
Neuroprotective effect of modified Tianma Gouteng Decoction on mice with intracerebral hemorrhage and its effect on the high-mobility group box 1/Toll-like receptor 4 signaling pathway
摘要
Abstract
Objective To investigate the effect of modified Tianma Gouteng Decoction on neuroinflammation and cell apoptosis in mice in the acute stage of intracerebral hemorrhage(ICH)and its association with the high-mobility group box 1(HMGB1)/Toll-like receptor 4(TLR4)signaling pathway.Methods A total of 32 male mice were randomly divided into sham-operation group(Sham group),ICH model group(ICH group),IT group(ICH mice treated with Tianma Gouteng Decoction),and ITG group(ICH mice treated with Tianma Gouteng Decoction and the HMGB1 target inhibitor glycyrrhizic acid),with 8 mice in each group.Mass spectrometry was used for drug quality control,and network pharmacology was used to perform target and pathway analyses.Intracerebral injection of collagenase VII was performed to establish a mouse model of ICH.Neurological deficit score and HE staining were used to observe the effect of Tianma Gouteng Decoction on neurological deficit and brain histopathological injury in mice after ICH;ELISA was used to measure the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β);Western blotting was used to measure the expression levels of Bcl-2-associated X protein(BAX),B-cell lymphoma-2(Bcl-2),HMGB1,TLR4,myeloid differentiation factor 88(Myd88),TIR-domain-containing adaptor-inducing interferon-β(TRIF),and nuclear factor-kappa B(NF-κB).Results Compared with the Sham group,the ICH group had exacerbation of neurological deficit and brain histopathological injury and increases in the levels of inflammatory markers and cell apoptosis,as well as increases in the expression levels of the pathway-related proteins HMGB1,TLR4,Myd88,TRIF,and NF-κB.Compared with the ICH group,the IT group and the ITG group had alleviation of neurological deficit and brain histopathological injury,reductions in the levels of inflammatory markers and cell apoptosis,and varying degrees of reductions in the expression levels of the pathway-related proteins HMGB1,TLR4,Myd88,TRIF,and NF-κB.In addition,509 compounds were obtained for Tianma Gouteng Decoction by mass spectrometry and network pharmacology,among which 75 were analyzed in terms of drug-likeness,and 195 molecular targets with a potential interventional effect were identified by target prediction.Gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis further verified the association of related molecular targets with inflammation and the HMGB1/TLR4 pathway.Conclusion Modified Tianma Gouteng Decoction can alleviate neurological deficit and brain histopathological injury in mice with ICH and reduce the levels of neuroinflammatory markers and cell apoptosis after ICH,possibly by inhibiting the expression of the HMGB1/TLR4 signaling pathway.关键词
脑出血/天麻钩藤饮/神经炎症/细胞凋亡/高迁移率族蛋白B1/Toll样受体4Key words
intracerebral hemorrhage/Tianma Gouteng Decoction/neuroinflammation/cell apoptosis/high-mobility group box 1/Toll-like receptor 4分类
医药卫生引用本文复制引用
刘泓,解茂芝,谭军,伍大华,陈博威,陶翠宁,罗春玉,袁春云..天麻钩藤饮加减对脑出血小鼠的神经保护作用及其对高迁移率组蛋白B1/Toll样受体4信号通路的影响[J].国际神经病学神经外科学杂志,2025,52(3):1-9,9.基金项目
湖南省自然科学基金(2023JJ60321) (2023JJ60321)
湖南省教育厅科学研究项目(20A381). (20A381)