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目的 探讨虾青素(AST)对草甘膦(GLY)尾静脉暴露所致小鼠脑神经损伤的缓解作用及其潜在机制。方法 将KM雄性小鼠随机分为对照组(CON)、草甘膦暴露组(GLY,1mg/kg尾静脉注射)和草甘膦暴露+虾青素治疗组(GLY+AST,GLY暴露后给予50mg/kg AST灌胃),连续给药35d。于给药第27d进行Morris水迷宫、旷场和高架十字迷宫行为学测试评估学习记忆及焦虑行为；第36d取脑组织，采用尼Nissl染色观察神经元形态变化；应用分子对接技术分析GLY、AST与β-位点淀粉样前体蛋白裂解酶1(BACE1)的结合活性；采用酶联免疫吸附试验(ELISA)检测脑组织中BACE1、β-淀粉样蛋白Aβ1-40及Aβ1-42水平。结果 行为学测试显示，GLY暴露组小鼠空间学习记忆能力显著下降、焦虑行为显著增加；Nissl染色显示GLY组海马等脑区神经元排列紊乱、尼氏体减少及坏死细胞比例升高；分子对接结果表明，GLY和AST均能与BACE1有效结合，结合能分别为-6.3 kcal/mol和-8.3 kcal/mol。ELISA检测显示，GLY组脑组织中BACE1、Aβ1-40及Aβ1-42水平较CON组显著升高(P均<0.05)。AST干预可显著改善上述行为学障碍，减轻神经元损伤，降低坏死细胞比例，并有效抑制GLY暴露引起的BACE1、Aβ1-40及Aβ1-42水平升高(P<0.05)。结论 草甘膦尾静脉暴露可诱导小鼠脑神经损伤及认知功能障碍，其机制可能与激活BACE1/Aβ通路有关；AST可通过抑制BACE1表达及Aβ生成，有效缓解草甘膦诱导的脑神经损伤。
Abstract：Objective To investigate the alleviating effect of astaxanthin(AST) on glyphosate(GLY)-induced brain neuroinjury in mice via tail vein injection and its underlying mechanisms.Methods KM male mice were randomly assigned into a control group(CON),a GLY exposure group(1 mg/kg via tail vein injection),and a GLY exposure + astaxanthin treatment group(GLY+AST,administered 50 mg/kg AST via gavage following GLY exposure).Continuous administration lasted for 35 days.On day 27 of administration, Morris water maze, open field, and elevated plus maze tests were conducted to assess learning and memory as well as anxiety-like behaviors.On day 36,brain tissues were collected.Nissl staining was employed to observe neuronal morphological changes.Molecular docking technology was utilized to analyze the binding activities of GLY and AST with β-site amyloid precursor protein cleaving enzyme 1(BACE1).Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of BACE1,and β-amyloid proteins Aβ1-40 and AβAβ1-42 in brain tissue.Results Behavioral tests revealed that GLY exposure significantly impaired spatial learning and memory, and increased anxiety-like behaviors in mice.Nissl staining showed disordered neuronal arrangement, reduced Nissl bodies, and an increased proportion of necrotic cells in the hippocampus and other brain regions of the GLY group.Molecular docking results demonstrated that both GLY and AST could effectively bind to BACE1,with binding energies of-6.3 kcal/mol and-8.3 kcal/mol, respectively.ELISA detection indicated that the levels of BACE1,Aβ1-40,and AβAβ1-42 in the brain tissue of the GLY group were significantly higher compared to the CON group(all P<0.05).AST intervention significantly ameliorated the behavioral impairments(P<0.05),alleviated neuronal damage, reduced the proportion of necrotic cells, and effectively suppressed the increases in BACE1,Aβ1-40,and Aβ1-42 levels induced by GLY exposure.Conclusion GLY exposure via tail vein injection can induce brain neuroinjury and cognitive dysfunction in mice, potentially involving the activation of the BACE1/Aβ pathway.AST can effectively alleviate GLY-induced brain neuroinjury by suppressing BACE1 expression and Aβ generation.
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基本信息:
DOI：10.16751/j.cnki.2095-4646.2025072001
中图分类号:R965
引用信息:
[1]马亚萍,张晓琳,王贝贝,等.虾青素缓解草甘膦诱导的小鼠脑神经损伤[J].湖北科技学院学报(医学版),2026,40(01):34-38+43.DOI:10.16751/j.cnki.2095-4646.2025072001.
基金信息:
湖北科技学院五官医学院专项科研基金(2020WG09);湖北科技学院横向项目(2024HX139)
2025-07-20
2025
2026-01-16
2026
2026-01-14
1
2026-01-20
2026-01-20