围产期PFOS暴露对幼鼠海马BDNF/TrkB/CREB信号通路影响

目的 探讨观察母孕鼠围产期全氟辛烷磺酸盐(perfluorooctane sulphonate,PFOS)暴露对幼鼠海马组织BDNF/TrkB/CREB信号通路关键基因表达的影响。 方法 20只昆明种雌性小鼠随机分为对照组和低、中、高剂量组,从孕鼠怀孕第2 d开始(gestation day2, GD2)到幼鼠出生后21 d(postnatal day21,PND21)分别给予低、中、高剂量组孕鼠PFOS剂量为 0.1、1.0、5.0 mg/(kg·bw)灌胃染毒,对照组给予等体积的0.05% Tween-20水溶液。灌胃量为0.1 ml/10 (g·bw)。PND 21 d处死幼鼠,收集脑组织,分离海马及皮层。HE染色观察脑组织常规病理改变,实时荧光定量PCR(Quantitative Real-time PCR,QPCR)检测海马组织中BDNF、TrkB、CREB、Syn1及Syp的mRNA表达水平。 结果 与对照组相比较,低、中、高三个剂量组对幼鼠的死亡率和体质量的影响差异无统计学意义(P>0.05)。但是在高剂量组幼鼠海马组织出现空泡,海马BDNF、TrkB、CREB mRNA水平显著降低,分别由对照组的(0.98±0.11)、(1.03±0.09)、(1.08±0.12)下降到(0.22±0.21)、(0.71±0.14)、(0.37±0.26),并在中、高剂量组引起了幼鼠突触相关蛋白Syn1和Spy的mRNA水平显著降低,分别由对照组的(1.10±0.09)、(0.97±0.08)下降到中剂量的(0.41±0.23)、(0.71±0.17)和高剂量的(0.39±0.19)、(0.63±0.19),差异均有统计学意义(P<0.05)。 结论 PFOS损伤海马BDNF/TrkB/CREB信号通路可能是PFOS神经发育毒性之一。

Effect of perinatal exposure to perfluorooctane sulfonate on BDNF/TrkB/CREB signaling pathways in hippocampus of mice offspring

Objective To explore the effect of perinatal exposure to perfluorooctane sulfonate (PFOS) on key gene expression of BDNF/TrkB/CREB signaling pathways in hippocampus of mice offspring. Methods Twenty pregnant Kunming mice were randomly divided into the control group and the low-, middle- and high-dose groups. The mice in the low-, middle- and high-dose groups were respectively administrated with 0.1, 1.0 and 5.0 mg/(kg·bw) PFOS by gavage from the gestation day 2 to the postnatal day 21. The control group received 0.05% Tween-20 solution. The gavage volume was 0.1 ml/10 (g·bw). The offspring’s brain tissues were collected and observed pathologically by hematoxylin-eosin (HE) staining on the postnatal day 21. Quantitative real-time PCR (QPCR) was used to detect mRNA expression levels of brain-derived neurotrophic factor (BDNF), tropomyosin-related receptor kinase B (TrkB), cAMP response element-binding protein (CREB), synapsin1 (Syn1) and synaptophysin (Syp) in hippocampus tissues. Results No statistically significant differences were found in the mortality rate and body weight of mice offspring between the control group and the low-, middle- and high-dose groups (P>0.05). However, vacuole was observed in offspring’s hippocampus tissues in the high-dose PFOS group. The mRNA levels of BDNF, TrkB and CREB in hippocampus tissues significantly decreased from (0.98±0.11), (1.03±0.09) and (1.08±0.12) in the control group to (0.22±0.21), (0.71±0.14) and (0.37±0.26), respectively. The mRNA levels of Syn1 and Syp in the middle- and high-dose PFOS groups also significantly decreased, which decreased from (1.10±0.09) and (0.97±0.08) in the control group to (0.41±0.23) and (0.71±0.17) in the middle-dose PFOS group and (0.39±0.19) as well as (0.63±0.19) in the high-dose PFOS group, showing statistically significant differences (all P<0.05). Conclusions PFOS can damage BDNF/TrkB/CREB signaling pathways in hippocampus tissues, which may be one of the mechanisms leading to developmental neurotoxicity of PFOS.