性成熟期间壬基酚诱导F1代大鼠神经毒性的机制。
Mechanism of nonylphenol-induced neurotoxicity in F1 rats during sexual maturity.
作者信息
Jie Yu, Xuefeng Yang, Mengxue Yang, Xuesong Yang, Jing Yang, Yin Tang, Jie Xu
机构信息
School of Public Health, Zunyi Medical University, 563000, Zunyi, Guizhou, P.R. of China.
Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University, 563000, Zunyi, Guizhou, P.R. of China.
出版信息
Wien Klin Wochenschr. 2016 Jun;128(11-12):426-34. doi: 10.1007/s00508-016-0960-6. Epub 2016 Feb 23.
OBJECTIVE
The purpose of this study was to examine whether gestational and lactational exposure to environmental endocrine disrupting chemical, nonylphenol (NP), in pregnant dams would lead to the alterations in hormone levels in the body, apoptosis and glial fibrillary acidic protein (GFAP) in hippocampus during weaning and sexual maturity periods in pups of rats.
METHODS
Dams were gavaged with NP at dose levels of 25 mg/kg/day (low dose), 50 mg/kg/day (middle dose), 100 mg/kg/day (high dose) and groundnut oil alone (vehicle control) respectively from gestational day 6 to postnatal day (PND) 21.
RESULTS
At PND 21, serum testosterone (TT) level significantly decreased in the 50, 100 mg/kg NP-treated groups compared with the control (p < 0.01). Serum estradiol (E2) level was increased with the increase in the NP concentration; a dose-effect relationship was revealed (r = 0.462, p < 0.01). At both PND 21 and PND 60, pups exposed to 100 mg/kg/day NP had an obviously higher apoptotic rate than control did. We observed a significant positive correlation between the dose of NP and the apoptotic rate (r = 0.836, p < 0.05). The number of GFAP-positive cells in rat hippocampus and integral optical density (IOD) of 100 mg/kg/day NP-treated group were much higher than the control group. GFAP mRNA expressions increased at high dose (100 mg/kg/day) (p < 0.05), and positive correlations between the GFAP mRNA expressions and NP level was observed (r = 0.586, 0.737, p < 0.05). Both the number of growth-associated protein (GAP)-43 positive cells and IOD were much lower at high dose (100 mg/kg/day) than the control at both PND 21 and PND 60 (p < 0.05). The number of GAP-43 positive cells was negatively correlated with the NP exposure dose (r = - 0.562, - 0.649, p < 0.05) at these two time points. GAP-43 mRNA expressions in the hippocampus of pups decreased dramatically at high dose (100 mg/kg/day) at both PND 21 and PND 60 compared with the control (p < 0.05).
CONCLUSION
High exposure to NP might inhibit neuronal development and differentiation as indicated by the reduction of the neurotrophic factor GAP-43.
目的
本研究旨在探讨孕期和哺乳期母鼠暴露于环境内分泌干扰化学物壬基酚（NP）是否会导致仔鼠断奶期和性成熟期体内激素水平改变、海马区细胞凋亡及胶质纤维酸性蛋白（GFAP）变化。
方法
从妊娠第6天至出生后第21天（PND 21），分别给母鼠灌胃NP，剂量为25 mg/kg/天（低剂量）、50 mg/kg/天（中剂量）、100 mg/kg/天（高剂量），单独灌胃花生油作为溶剂对照。
结果
在PND 21时，与对照组相比，50、100 mg/kg NP处理组的血清睾酮（TT）水平显著降低（p＜0.01）。血清雌二醇（E2）水平随NP浓度增加而升高，呈现剂量 - 效应关系（r = 0.462，p＜0.01）。在PND 21和PND 60时，暴露于100 mg/kg/天NP的仔鼠凋亡率均明显高于对照组。NP剂量与凋亡率之间存在显著正相关（r = 0.836，p＜0.05）。100 mg/kg/天NP处理组大鼠海马区GFAP阳性细胞数量和积分光密度（IOD）均显著高于对照组。高剂量（100 mg/kg/天）时GFAP mRNA表达增加（p＜0.05），且GFAP mRNA表达与NP水平之间存在正相关（r = 0.586，0.737，p＜0.05）。在PND 21和PND 60时，高剂量（100 mg/kg/天）组生长相关蛋白（GAP）-43阳性细胞数量和IOD均显著低于对照组（p＜0.05）。在这两个时间点，GAP-43阳性细胞数量与NP暴露剂量呈负相关（r = -0.562，-0.649，p＜0.05）。与对照组相比,在PND 21和PND 60时，高剂量（100 mg/kg/天）组仔鼠海马区GAP-43 mRNA表达均显著降低（p＜0.05）。
结论
高剂量NP暴露可能通过降低神经营养因子GAP-43抑制神经元的发育和分化。
Zotero 插件