高效氟氯氰菊酯基于雌激素膜受体通路干扰小鼠海马神经发育的体外研究  

Lambda-cyhalothrin influences hippocampal neurodevelopment in mice via estrogen membrane receptor pathway

作　　者：夏新 王岩[1] 吴同俊[1] 滕晶晶[1] 张玉媛 邓晓媚 王取南[4] XIA Xin;WANG Yan;WU Tong-jun;TENG Jing-jing;ZHANG Yu-yuan;DENG Xiao-mei;WANG Qu-nan(Toxicology laboratory,Anhui Provincial Center for Disease Control and Prevention,Hefei Anhui 230601,China;School of Public Health,Bengbu Medical College,Bengbu Anhui 233030,China;Department of Pharmacy,The First Affliated Hospital of University of Science and Technology of China,Hefei Anhui 230036,China;College of Public Health,Anhui Medical University,Hefei Anhui 230032,China)

机构地区：[1]安徽省疾病预防控制中心毒理实验室,安徽合肥230601 [2]蚌埠医学院公共卫生学院,安徽蚌埠233030 [3]中国科学技术大学附属第一医院药学部,安徽合肥230036 [4]安徽医科大学公共卫生学院,安徽合肥230032

出　　处：《毒理学杂志》2022年第5期402-407,413,共7页Journal of Toxicology

基　　金：安徽省卫健委科研课题(2017jk007)。

摘　　要：目的 探讨高效氟氯氰菊酯(lambda-cyhalothrin, LCT)是否通过雌激素膜受体影响小鼠海马神经发育及其相关机制。方法 使用原代小鼠海马神经细胞和HT22细胞系,以雌激素(Estrogen, E2,1 nmol/L)作为阳性对照,分别使用LCT(1μmol/L)、雌激素膜受体激动剂G1(1 nmol/L)和雌激素膜受体抑制剂G15(1 nmol/L)处理24 h,观察原代神经细胞突起、突触后致密蛋白95(post-synaptic density protein 95,PSD95)表达,并检测HT22细胞外调节蛋白激酶(extracellular regulated protein kinases, ERK)、c-Jun氨基末端激酶(c-Jun N-terminal kinase, JNK)通路的活化。结果 LCT、E2和G1均促进神经突起发育和PSD95表达(P<0.05),LCT和G1可以上调JNK磷酸化水平(P<0.05),G15抑制该促进作用(P<0.05);E2上调了ERK磷酸化水平(P<0.05)。结论 LCT可以产生类似G1的作用影响神经发育,且与E2促神经发育的机制并不完全一致。Objective To investigate the effect of lambda cyhalothrin(LCT) on the development of hippocampal neurons in vitro. Methods The primary mouse hippocampal neuron culture model and HT22 cell model were used, and then exposed to LCT(1 μmol/L), estrogen(E2)(1 nmol/L)and estrogen membrane receptor agonist G1(1 nmol/L), antagonist G15(1 nmol/L) for 24 hours. The expressions of post-synaptic density protein 95(PSD95) and the development of neurite were detected using Immunofluorescence cytochemistry in primary hippocampal neurons. Western blot was used for detecting the activation of ERK and JNK pathway in HT22 cells. Results LCT, E2 and G1 can promote neurite development and PSD95 expression, G15 can inhibit the effect, LCT and G1 can up-regulate JNK phosphorylation, and E2 can up-regulate ERK phosphorylation. Conclusion LCT can produce a similar effect with G1 on neurodevelopment, which is not consistent with the mechanism of E2.

关 键 词：高效氟氯氰菊酯 雌激素膜受体通路 神经发育 

分 类 号：R114[医药卫生—卫生毒理学] R994[医药卫生—公共卫生与预防医学]