黄芩素调控NRG1/ErbB4通路对血管性痴呆大鼠认知功能及海马神经元的影响OA
Impacts of baicalein on cognitive function and hippocampal neuron in vascular dementia rats by adjusting NRG1/ErbB4 pathway
目的:探讨黄芩素调控神经调节蛋白1(NRG1)/Erb-B2 受体酪氨酸蛋白激酶4(ErbB4)通路对血管性痴呆(VD)大鼠认知功能及海马神经元的影响.方法:10 只正常 SD 大鼠为假手术组.将40 只 VD 模型 SD 大鼠随机分为 VD 组、低剂量黄芩素(50 mg/kg)组、高剂量黄芩素(100 mg/kg)组、高剂量黄芩素+达克替尼(NRG1/ErbB4通路抑制剂,7.5 mg/kg)组,每组10 只,均为灌胃给药.采用 Zea-Longa 评分和 Morris 水迷宫实验评估大鼠神经功能,ELISA 法检测大鼠血清 TNF-α、IL-6 和 IL-1β 水平,HE 染色和透射电镜分别观察大鼠海马组织形态和超微结构,硫代巴比妥酸法、比色法及羟胺法分别检测海马组织 MDA 含量、谷胱甘肽过氧化物酶(GSH-PX)活性、SOD 活性,Western blot 法检测海马组织脑源性神经营养因子(BDNF)、Cleaved-caspase-3、髓鞘碱性蛋白(MBP)、少突胶质细胞转录因子1(Olig1)、NRG1/ErbB4 通路蛋白的表达.结果:与假手术组相比,VD 组大鼠海马组织神经元间隙增大,细胞空泡变性、胞核固缩,线粒体肿胀、数量减少,逃避潜伏期,血清 TNF-α、IL-1β 和 IL-6 水平,海马组织 MDA含量和 Cleaved-caspase-3 蛋白表达水平升高,目标象限滞留时间,平台穿越次数,海马组织 SOD 和 GSH-PX 活性、BDNF、MBP、Olig1、NRG1 和 p-ErbB4/ErbB4 蛋白表达水平降低(P<0.05);与 VD 组比较,低、高剂量黄芩素组海马组织和神经元形态以及上述其他检测指标均有改善(P<0.05);达克替尼可减弱黄芩素对 VD 大鼠神经功能障碍和神经元损伤的改善作用(P<0.05).结论:黄芩素可减轻 VD 大鼠炎症、氧化应激和神经元损伤,改善神经功能,其机制可能与激活 NRG1/ErbB4 通路有关.
Aim:To investigate the effects of baicalein on cognitive function and hippocampal neuron in rats with vas-cular dementia(VD)and to explore whether these effects are mediated through the regulation of neuregulin-1(NRG1)/erb-b2 receptor tyrosine kinase 4(ErbB4)pathway.Methods:Forty SD rats were established VD models and randomly assigned into 4 groups(n=10 each):VD group,low-dose baicalein group,high-dose baicalein group,and high-dose baicalein plus dacomitinib(an NRG1/ErbB4 pathway inhibitor,7.5 mg/kg)group.An additional sham operation group(n=10)was in-cluded.All treatments were administered via intragastric gavage.Neurological function was assessed using the Zea-Longa score and the Morris water maze test.Serum levels of TNF-α,IL-6,and IL-1β were measured by ELISA.Hippocampal histo-morphological changes and ultrastructural alterations were observed using HE staining and transmission electron microscopy,respectively.Malondialdehyde(MDA)content,glutathione peroxidase(GSH-PX)activity,and superoxide dismutase(SOD)activity in hippocampal tissues were determined via thiobarbituric acid method,colorimetric method,and hydroxylamine method,respectively.Protein expression levels of brain-derived neurotrophic factor(BDNF),Cleaved-caspase-3,myelin bas-ic protein(MBP),oligodendrocyte transcription factor1(Olig1),NRG1,and p-ErbB4/ErbB4 in the hippocampus were de-tected by Western blot.Results:Compared with the sham operation group,the VD group exhibited significantly enlarged in-ter-neuronal spaces,vacuolar degeneration,pyknotic nuclei,swollen and reduced mitochondria in hippocampal neurons,pro-longed escape latency,elevated serum levels of TNF-α,IL-1β,and IL-6,increased hippocampal MDA content and Cleaved-caspase-3 protein expression,alongside decreased target quadrant dwell time,number of platform crossings,hippocampal SOD and GSH-PX activities,and protein expression levels of BDNF,MBP,Olig1,NRG1,and p-ErbB4/ErbB4 ratio(all P<0.05).Compared with the VD group,both low-and high-dose baicalein groups showed significant improvements in hipp-ocampal tissue and neuronal morphology,as well as in all the above-mentioned parameters(P<0.05).Notably,co-adminis-tration of dacomitinib significantly attenuated the beneficial effects of baicalein on neurological dysfunction and neuronal in-jury in VD rats(P<0.05).Conclusion:Baicalein alleviates inflammation,oxidative stress,and neuronal injury,and im-proves neurological function in VD rats,potentially through the activation of the NRG1/ErbB4 pathway.
刘欢;肖骋
咸宁市中心医院(湖北科技学院附属第一医院)神经内科 湖北 咸宁 437100咸宁市中心医院(湖北科技学院附属第一医院)神经内科 湖北 咸宁 437100
医药卫生
黄芩素NRG1/ErbB4通路血管性痴呆神经保护大鼠
baicaleinNRG1/ErbB4 pathwayvascular dementianeuroprotectionrat
《郑州大学学报（医学版）》 2026 (4)
40-44,5
咸宁市市级科技计划项目(2020ZRKX03)
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