生命早期暴露全氟丁烷磺酸对SD大鼠的神经发育毒性及其机制  

Developmental neurotoxicity and its mechanism of perfluorobutane sulfonate exposure in early life in SD rats

作　　者：谭启涛 朱航宇 孙艳 TAN Qitao;ZHU Hangyu;SUN Yan(School of Public Health,Guilin Medical College,Guilin 541199,Guangxi,China)

机构地区：[1]桂林医学院公共卫生学院,广西桂林541199

出　　处：《癌变.畸变.突变》2025年第1期21-26,共6页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：广西自然科学基金(2023GXNSFAA026035)。

摘　　要：目的:研究生命早期暴露全氟丁烷磺酸(PFBS)对SD大鼠子代神经发育的影响,并探讨其机制。方法:将受孕SD母鼠随机分为4组,每组5只,分别为对照组(0 mg/kg,生理盐水)和PFBS低(5 mg/kg)、中(50 mg/kg)、高剂量组(500 mg/kg)。在母鼠受孕第2天开始经口灌胃染毒至仔鼠断乳。仔鼠日龄90 d后,每个剂量组随机挑选10只仔鼠处死并取材。光镜下观察仔鼠海马体组织病理学变化;Western blot法检测仔鼠海马体中BDNF、TRKB、PI3K、AKT及P-AKT的蛋白表达水平;逆转录荧光定量PCR(RT-qPCR)法检测Syn1和Syp mRNA的相对表达水平。结果:病理学检测结果显示各个PFBS暴露组仔鼠的海马体均受到损伤,其中高剂量组仔鼠的海马体损伤最严重。Western blot检测结果显示,与对照组相比,各个PFBS暴露组仔鼠的BDNF、TRKB、PI3K、P-AKT蛋白表达水平下调(P<0.01),P-AKT/AKT蛋白表达水平的比值降低(P<0.05)。RT-qPCR检测结果显示,与对照组相比,中剂量组和高剂量组的CREB下游基因Syn1与Syp的mRNA表达水平下调(P<0.05或P<0.01)。结论:生命早期PFBS暴露对大鼠的海马体造成损伤;PFBS损伤海马体BDNF/TRKB/CREB及PI3K/AKT信号通路可能是PFBS的神经发育毒性机制。OBJECTIVE:This study aimed to investigate the effects from exposure to perfluorobutanesulfonic acid(PFBS)on the neurodevelopment of rat offspring.METHODS:Maternal rats were divided into PFBS low(5 mg/kg),medium(50 mg/kg),high(500 mg/kg)dose groups and control group(saline).The rats were dosed from the second day of pregnancy(GD1)until weaning.At 90 days after birth,10 offspring from each group were randomly selected for sacrificing,and the hippocampal tissue was collected for pathological,Western blot,and real-time qPCR tests.Pathological test was used to observe the impair of CA1 of hippocampus by subjecting to hematoxylin-eosin(HE)staining.Protein expression of BDNF,TRKB,PI3K,AKT and P-AKT in hippocampus were detected by Western blot.The expression level of Syn1 and Syp mRNA in hippocampus were detected by quantitative reverse transcription PCR.RESULTS:The pathological test showed that early-life exposure to PFBS resulted in the nuclear condensation,blurred cell boundaries,and irregular cell morphology in the CA1 region of hippocampus in each dose groups,most significant in the high dose group.Compared to the control group,protein expression of BDNF,TRKB,PI3K,P-AKT and the ratio of P-AKT/AKT were decreased in each dose group(P<0.01).Expression levels of Syn1 and Syp mRNA decreased in the medium and high dose groups,compared to control group(P<0.05).CONCLUSION:Exposed to PFBS during early life damaged the hippocampus.Damage from PFBS on the BDNF/TRKB/CREB and PI3K/AKT signaling pathways might be the mechanisms for induction of developmental neurotoxicity in rats.

关 键 词：全氟和多氟烷基类化合物 全氟丁烷磺酸 生命早期 神经发育毒性 BDNF/CREB通路 

分 类 号：R994.6[医药卫生—毒理学]