世界中医药2025,Vol.20Issue(10):1686-1693,8.DOI:10.3969/j.issn.1673-7202.2025.10.007
牛蒡子苷元调控铁死亡对急性脑梗死大鼠神经功能的保护作用
Protective Effect of Arctigenin on Neurological Function in Rats with Acute Cerebral Infarction by Regulating Ferroptosis
摘要
Abstract
Objective:To investigate the neuroprotective effects of arctigenin(ARG)against neurological impairment in acute cere-bral infarction(ACI)rats by regulating ferroptosis.Methods:An ACI rat model was established using middle cerebral artery occlu-sion(MCAO)via the intraluminal suture method.After successful model induction,rats were randomly divided into five groups(n=15 per group):sham-operated group(0.9%saline,i.p.),model group(0.9%saline,i.p.),low-dose ARG group(3.0 mg/kg,i.p.),high-dose ARG group(12.0 mg/kg,i.p.),and high-dose ARG+ML385 group(ARG 12.0 mg/kg+ML385 30 mg/kg,i.p.).All treatments were administered for 7 consecutive days.Neurological deficits and infarct volume were assessed after interven-tion.Histopathological changes in brain tissue were evaluated by hematoxylin-eosin(HE)staining,iron ion level and deposition by Prussian blue staining,oxidative stress indicators in brain tissue by biochemical assays,reactive oxygen species(ROS)levels by di-hydroethidium(DHE)staining,neuronal apoptosis by TUNEL staining,and neuronal mitochondrial ultrastructure by transmission e-lectron microscopy.The expression of ferroptosis-related proteins and the Nrf2/HO-1 signaling pathway proteins in brain tissue were detected by Western blot.Results:Compared with the sham-operated group,the model group showed significantly increased neuro-logical deficit scores,infarct volume,neuronal apoptosis rate,ROS levels,oxidative stress markers,and ferroptosis levels(P<0.05),along with significantly decreased expression of Nrf2/HO-1 pathway proteins(P<0.05),and obvious neuronal and mito-chondrial damage.Compared with the model group,both low-and high-dose ARG treatment significantly activated the Nrf2/HO-1 pathway,reduced infarct volume(P<0.05)and neuronal apoptosis rate(P<0.05),decreased ROS and oxidative stress levels(P<0.05),inhibited neuronal ferroptosis(P<0.05),restored neuronal and mitochondrial morphology,and improved neurological function.Compared with the high-dose ARG group,co-administration of ML385 reversed the neuroprotective effects of ARG in ACI rats.Conclusion:ARG alleviates neurological impairment in ACI rats,likely through activation of the Nrf2/HO-1 signaling pathway to inhibit neuronal ferroptosis.关键词
急性脑梗死/大鼠/牛蒡子苷元/神经元/铁死亡/神经功能/核因子E2相关因子2/血红素加氧酶-1/氧化应激Key words
Acute cerebral infarction/Rats/Arctigenin/Neuron/Ferroptosis/Neurological function/Nuclear factor E2-related factor 2/heme oxygenase-1/Oxidative stress分类
医药卫生引用本文复制引用
刘俊芳,张华锴..牛蒡子苷元调控铁死亡对急性脑梗死大鼠神经功能的保护作用[J].世界中医药,2025,20(10):1686-1693,8.基金项目
国家自然科学基金项目(82000775) (82000775)
河南省中医药科学研究专项(2019zY1016) (2019zY1016)