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目的在世界范围内受砷中毒影响的国家十分广泛,环境砷暴露可严重损害儿童的智力发育。白藜芦醇（resveratrol,Res）具有广泛的生物学效应,包括抗炎、抗氧化和神经保护作用,但其对砷暴露所致学习记忆功能损害的影响尚未阐明。本研究建立了子代小鼠砷暴露动物模型,给予Res进行干预,明确Res对砷致学习记忆损伤的保护作用及与磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase,PI3K）/蛋白激酶B（protein kinase B,Akt）/核转录因子-κB（nuclear transcription factor-κB,NF-κB）信号转导通路相关的机制,并进一步观察蛋白激酶A（protein kinase A,PKA）、环磷酸腺苷反应元件结合蛋白（c AMP Response element-binding protein,CREB）、突触素（synaptophysin,SYP）和突触后致密物95（postsynaptic density95,PSD95）改变,为指导地方性砷中毒的防治工作提供理论依据。方法妊娠第1d,36只孕鼠随机分为饮蒸馏水组（12只）和砷暴露组（24只）,采用自由饮水方式染砷。仔鼠通过母体和饮水染砷,出生后28 d给予Res进行灌胃干预4 w,来自饮蒸馏水组窝别的仔鼠随机分为对照组和50 mg/kg Res组,来自砷暴露组窝别的仔鼠随机分为60 mg/L Na As O2组、60 mg/L Na As O2+（25、50和100 mg/kg）Res组,每个实验项目选取每组6只仔鼠,通过Morris水迷宫实验检测仔鼠的空间学习记忆能力,采用HE染色观察仔鼠海马神经细胞形态改变,采用Real-time RT-PCR检测PI3K、Akt、NF-κB P65、SYP和PSD95 m RNA水平,应用Western blot法检测PI3K、p-Akt、NF-κB P65、p-NF-κB P65、PKA、CREB、SYP和PSD95蛋白表达水平。结果各组仔鼠的体重、脑重和海马重差异均无统计学意义。Morris水迷宫实验检测发现在定位航行实验训练的第4天和第5天,Na As O2组寻找平台潜伏期明显长于对照组,与Na As O2组相比,Na As O2+Res25和Na As O2+Res50组仔鼠寻找平台潜伏期在训练第4天显著缩短,Na As O2+不同浓度Res组仔鼠寻找平台潜伏期在训练第5天也均显著缩短（P＜0.05）;在空间探索实验中,Na As O2组仔鼠在目标象限停留时间和穿越平台次数显著少于对照组（P＜0.05）,Na As O2+Res25和Na As O2+Res50组仔鼠在目标象限停留时间明显长于Na As O2组,Na As O2+不同浓度Res组仔鼠在目标象限穿越次数明显增多（P＜0.05）。HE染色观察海马CA1和CA3区发现,Na As O2组仔鼠海马神经细胞数量减少,细胞形态受损,细胞碎裂,而Na As O2+不同浓度Res组仔鼠海马组织神经细胞数量增加,细胞形态改善。Real-time RT-PCR结果显示,Na As O2组仔鼠海马PI3K、Akt、NF-κB P65、SYP和PSD95 m RNA水平均明显低于对照组（P＜0.05）,Na As O2+Res50和Na As O2+Res100组仔鼠海马PI3K m RNA水平明显高于Na As O2组和Na As O2+Res25组（P＜0.05）,Na As O2+不同浓度Res组仔鼠海马Akt和PSD95m RNA水平均明显高于Na As O2组（P＜0.05）,且Na As O2+Res25和Na As O2+Res50组仔鼠海马Akt m RNA水平明显高于Na As O2+Res100组,Na As O2+Res50组仔鼠海马NF-κB P65 m RNA水平明显高于Na As O2组和Na As O2+Res25组（P＜0.05）,Na As O2+Res25和Na As O2+Res50组仔鼠海马SYP m RNA水平明显高于Na As O2组和Na As O2+Res100组（P＜0.05）。Western blot结果显示,Na As O2组仔鼠海马PI3K、p-Akt、p-NF-κB P65/NF-κB P65、PKA、CREB、SYP和PSD95蛋白表达水平均明显低于对照组（P＜0.05）,Na As O2+不同浓度Res组仔鼠海马PI3K和PSD95蛋白表达水平明显高于Na As O2组（P＜0.05）,Na As O2+Res50和Na As O2+Res100组仔鼠海马p-NF-κB P65/NF-κB P65蛋白表达水平明显高于Na As O2组（P＜0.05）,Na As O2+Res25组仔鼠海马p-Akt蛋白表达水平明显高于Na As O2组和Na As O2+Res100组（P＜0.05）,Na As O2+Res100组仔鼠海马SYP蛋白表达水平明显高于Na As O2组、Na As O2+Res25组和Na As O2+Res50组（P＜0.05）,Na As O2+Res25和Na As O2+Res100组仔鼠海马PKA和CREB蛋白表达水平均明显高于Na As O2组和Na As O2+Res50组（P＜0.05）,结论1.Res可改善砷暴露导致的仔鼠学习与记忆能力损伤。2.砷暴露可使子代小鼠海马中PI3K、Akt和NF-κB基因和蛋白表达水平降低,从而可能影响PI3K/Akt/NF-κB信号通路。3.Res干预可能通过影响PI3K/Akt/NF-κB信号通路而改善砷暴露所致的仔鼠学习记忆功能损害。