吕胜杰, 宁丽俊, 王琦, 聂继盛. 孕期苯并[a]芘暴露对子鼠神经行为及海马Arc mRNA表达的影响[J]. 环境与职业医学, 2019, 36(2): 128-133. DOI: 10.13213/j.cnki.jeom.2019.18434
引用本文: 吕胜杰, 宁丽俊, 王琦, 聂继盛. 孕期苯并[a]芘暴露对子鼠神经行为及海马Arc mRNA表达的影响[J]. 环境与职业医学, 2019, 36(2): 128-133. DOI: 10.13213/j.cnki.jeom.2019.18434
LÜ Sheng-jie, NING Li-jun, WANG Qi, NIE Ji-sheng. Effects of prenatal benzo[a]pyrene exposure on neurobehavior and Arc mRNA expression in hippocampus of offspring rats[J]. Journal of Environmental and Occupational Medicine, 2019, 36(2): 128-133. DOI: 10.13213/j.cnki.jeom.2019.18434
Citation: LÜ Sheng-jie, NING Li-jun, WANG Qi, NIE Ji-sheng. Effects of prenatal benzo[a]pyrene exposure on neurobehavior and Arc mRNA expression in hippocampus of offspring rats[J]. Journal of Environmental and Occupational Medicine, 2019, 36(2): 128-133. DOI: 10.13213/j.cnki.jeom.2019.18434

孕期苯并a芘暴露对子鼠神经行为及海马Arc mRNA表达的影响

Effects of prenatal benzoapyrene exposure on neurobehavior and Arc mRNA expression in hippocampus of offspring rats

  • 摘要: 目的 以苯并a芘(BaP)为代表的多环芳烃所引起的儿童发育毒性可能是一个非常重要的公共卫生问题,而有研究显示,海马活性调控骨架相关蛋白(Arc)基因对出生后神经发生和学习记忆发挥着重要作用。本研究拟探讨孕期BaP暴露对子鼠神经行为和Arc mRNA表达的影响。

    方法 3月龄健康SPF级SD大鼠60只(雌雄比例为1:1),合笼交配后将30只怀孕SD大鼠随机分为空白组、橄榄油组和10、20、40 mg/kg BaP染毒组,每组6只。BaP由橄榄油溶解,母鼠受孕第17、18、19天按体重腹腔注射染毒,每天1次,连续3 d,给药体积0.2 mL/kg;橄榄油组注射相同体积的橄榄油;空白对照组不给任何处理。比较各组子鼠出生后第7天(postnatal day 7,PND7)悬崖回避、PND14空中翻正的达标率情况,以及PND37的水迷宫实验结果,即逃避潜伏期、目标象限停留时间和穿越平台数。观察子鼠PND1、PND7、PND14、PND45海马Arc mRNA水平。

    结果 在PND7,与橄榄油组(97.56%)相比,20 mg/kg染毒组(63.64%)和40 mg/kg染毒组(60.98%)悬崖回避实验的达标率下降(P < 0.05)。在PND14,与橄榄油组(65.71%)相比,40 mg/kg染毒组(29.73%)空中翻正达标率下降(P < 0.05)。水迷宫定位航行实验结果显示:与橄榄油组相比,BaP染毒组PND37在实验的第1、3、4天的逃避潜伏期升高(P < 0.05)。空间探索实验结果显示,与橄榄油组相比,BaP染毒组PND37目标象限停留时间和穿越平台数减少(P < 0.05)。对不同时点的海马Arc mRNA的表达水平检测结果显示:与橄榄油组相比,3个BaP染毒组在PND1、PND7的Arc mRNA均降低(P < 0.05);在PND14,与橄榄油组(14.86±2.48)对比,40 mg/kg染毒组(7.31±1.94)Arc mRNA降低(P < 0.05);在PND45,与橄榄油组(39.66±6.39)对比,40mg/kg染毒组(19.98±8.21)Arc mRNA降低(P < 0.05)。

    结论 孕期BaP暴露会引起子鼠的早期神经行为异常及发育后期空间学习记忆能力下降,而海马的Arc mRNA表达下降可能参与了BaP神经发育毒性的发生。

     

    Abstract: Objective The developmental toxicity caused by polycyclic aromatic hydrocarbons represented by benzoapyrene (BaP) is a major public health concern. However, studies show that the gene of activity regulated cytoskeleton associated protein (Arc) plays an important role in neurogenesis and learning and memory of offspring. This article aims to investigate the effects of prenatal BaP exposure on neurobehavior and mRNA expression of Arc in hippocampus of offspring rats.

    Methods Sixty healthy 3-month-old SPF SD rats (male:female=1:1) were mated, and the 30 pregnant rats were randomly divided into blank control group, olive oil group, and 10, 20, and 40 mg/kg BaP groups, and each group contained six rats. BaP was administrated intraperitoneally at 0.2 mL/kg in terms of weight at 17, 18, and 19 days after pregnancy once a day for 3 consecutive days, olive oil was used as solvent control, while the blank control group did not receive any administration. The attainment rates of cliff avoidance on postnatal day 7 (PND7) and air righting reflex on PND14, as well as escape latency, time spent in the target quadrant, and number of crossing platforms on PND37 were counted. The mRNA levels of Arc in hippocampus on PND1, PND7, PND14, and PND45 were measured.

    Results On PND7, compared with the olive oil group (97.56%), the cliff avoidance attainment rates of the 20 mg/kg BaP group (63.64%) and the 40 mg/kg BaP group (60.98%) decreased (P < 0.05). On PND14, compared with the olive oil group (65.71%), the attainment rate of air righting reflex of the 40 mg/kg group (29.73%) decreased (P < 0.05). The results of place navigation test showed that compared with the olive oil group, the escape latencies on days 1, 3, and 4 of testing in the groups administrated with BaP were significantly increased (P < 0.05). The results of probe trial showed that compared with the olive oil group, the time spent in target quadrant and the number of crossing platforms on PND37 in the groups administrated with BaP were significantly reduced (P < 0.05). For hippocampal Arc mRNA expression level at different time points, on PND1 and PND7, compared with the olive oil group, the Arc mRNA expression levels of all the BaP administered groups were significantly lower (P < 0.05); on PND14, compared with the olive oil group (14.86±2.48), the Arc mRNA expression level of the 40 mg/kg group (7.31±1.94) was reduced significantly (P < 0.05); on PND45, there was a statistically significant decrease in Arc mRNA level in the 40 mg/kg BaP group (19.98±8.21) compared with the olive oil group (39.66±6.39) (P < 0.05).

    Conclusion Prenatal BaP exposure can cause offspring abnormal neurobehavior in early life and defected spatial learning and memory ability in late stage of development, and declined Arc mRNA in hippocampus may participate in inducing the neurodevelopmental toxicity of BaP.

     

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