中国实验方剂学杂志2026，Vol.32Issue(11)：68-76,9.DOI:10.13422/j.cnki.syfjx.20260523
黄连解毒汤通过抑制NF-κB信号通路调控神经元改善缺血性脑卒中后认知功能障碍
Huanglian Jiedutang Improves Cognitive Impairment after Schemic Stroke by Regulating Neuron via NF-κB Signaling Pathway
摘要
Abstract
Objective:To investigate the effects of Huanglian Jiedutang(HLJDT)on cognitive function in mice with ischemic stroke(IS)and to elucidate whether its neuroprotective effects are mediated by inhibition of the nuclear factor-κB(NF-κB)signaling pathway and subsequent suppression of NF-κB-regulated neuronal apoptosis.Methods:An IS model was established using middle cerebral artery occlusion(MCAO).Sixty C57BL/6J mice were randomly assigned to five groups(n=12 per group),i.e.,sham operation,model,HLJDT low-dose(3.9 g·kg-1·d-1),HLJDT high-dose(7.8 g·kg-1·d-1),and Ginkgo biloba extract(GBE,31.2 mg·kg-1·d-1).Post-operatively,neurological deficit scores(Longa score),cerebral infarct volume assessed by 2,3,5-triphenyltetrazolium chloride(TTC)staining,and brain water content were evaluated.Learning and memory were assessed using new object recognition(NOR)and fear conditioning(FC)tests.Hippocampal pathology was examined via hematoxylin and eosin(HE)staining.Immunofluorescence detected expression of glial fibrillary acidic protein(GFAP,astrocyte marker),cellular oncogene Fos(c-Fos,neuronal activation marker),and glutamate decarboxylase 65(GAD65).Western blot measured nuclear factor-κB inhibitor protein α(IκBα),phosphorylated IκBα(p-IκBα),NF-κB p65,phosphorylated NF-κB p65(p-NF-κB p65),ionic calcium binding adapter molecule 1(Iba-1),tumor necrosis factor(TNF)-α,interleukin(IL)-1β,and apoptosis-related proteins,such as cleaved cysteinyl aspartate-specific protease 3(Caspase-3),B-cell lymphoma 2(Bcl-2),and Bcl-2-associated X protein(Bax).Real-time quantitative PCR(Real-time PCR)was used to assess mRNA levels of Iba-1,TNF-α,IL-1β,NF-κB p65,cleaved Caspase-3,Bax,and Bcl-2.Results:Compared with the sham group,the model group exhibited significantly increased neurological deficit scores,brain water content,and cerebral infarct volume(P＜0.01).Hippocampal CA1 neurons were disorganized,showing nuclear pyknosis and karyolysis.NOR exploration time and FC freezing time were significantly reduced(P＜0.01).GFAP and c-Fos expression were increased,while GAD65 expression was decreased(P＜0.01).Cleaved Caspase-3 and Bax were upregulated,Bcl-2 was downregulated,and the Bax/Bcl-2 ratio was elevated(P＜0.01).Expression levels of p-IκBα,p-NF-κB p65,IL-1β,TNF-α,and Iba-1 were significantly increased(P＜0.01).Compared with the model group,HLJDT high-dose,low-dose,and GBE groups showed significant improvements in all parameters(P＜0.01).Among them,the HLJDT high-dose group showed the most pronounced neuronal structural recovery and superior performance in NOR and FC tests(P＜0.01).In this group,GFAP and c-Fos decreased,GAD65 increased(P＜0.01),apoptosis-related protein expression was reversed,and NF-κB signaling and related inflammatory factor expression were suppressed(P＜0.01).Conclusion:HLJDT ameliorates cognitive dysfunction in mice after IS,potentially by inhibiting the NF-κB signaling pathway,thereby reducing neuroinflammation and hippocampal neuronal apoptosis.关键词
黄连解毒汤/缺血性脑卒中/核转录因子(NF)-κB信号通路/神经炎症/细胞凋亡/认知功能障碍/海马Key words
Huanglian Jiedutang/ischemic stroke/nuclear factor-κB(NF-κB)signaling pathway/neuroinflammation/apoptosis/cognitive impairment/hippocampus分类
医药卫生引用本文复制引用
孙梦颖,刘志龙,王俪臻,李彤,王磊磊,贾世艳,王婷婷,杨延雯,司凯强,崔友祥..黄连解毒汤通过抑制NF-κB信号通路调控神经元改善缺血性脑卒中后认知功能障碍[J].中国实验方剂学杂志,2026,32(11):68-76,9.基金项目
国家自然科学基金项目(U21A20400) （U21A20400）
国家中医药传承创新发展示范试点项目(沧卫中医[2023]16号) （沧卫中医[2023]16号）
河北省自然科学基金项目(H2024110042) （H2024110042）
河北省中西医结合神经康复重点实验室项目(SZX201318) （SZX201318）
硕士研究生校级创新资助立项项目(XCXZZSS2025002) （XCXZZSS2025002）
