溴氰菊酯诱导海马神经元MEK/ERK信号通路和细胞凋亡致小鼠神经行为障碍  

Deltamethrin induces hippocampal neuronal MEK/ERK signaling pathway and apoptosis leading to neurobehavioral disorders in mice

作　　者：吴敏嘉 陈阳 马佩璇 韦乐幸 潘雯 邓雅琴 陈维奇 黄晓薇[1,2,3] WU Minjia;CHEN Yang;MA Peixuan;WEI Lexing;PAN Wen;DENG Yaqin;CHEN Weiqi;HUANG Xiaowei(Department of Toxicology,School of Public Health,Guangxi Medical University,Nanning 530021,China;Guangxi Key Laboratory of Environment and Health Research,Nanning 530021,China;Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases,Nanning 530021,China)

机构地区：[1]广西医科大学公共卫生学院毒理学系,南宁530021 [2]广西环境与健康研究重点实验室,南宁530021 [3]广西高校高发疾病预防与控制研究重点实验室,南宁530021

出　　处：《广西医科大学学报》2025年第1期39-46,共8页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.21966010);广西医科大学高水平创新团队及杏湖学者计划项目。

摘　　要：目的:探究MEK/ERK信号通路和细胞凋亡在溴氰菊酯(DM)短期暴露致神经毒性的潜在作用及分子机制。方法:将40只成年雄性C57BL/6J小鼠随机分为对照组、DM低剂量组(4.5 mg/kg)、DM中剂量组(9.0 mg/kg)和DM高剂量组(18.0 mg/kg),连续灌胃30 d,对照组给予等容量玉米油。采用Morris水迷宫实验检测小鼠的学习记忆能力,苏木精—伊红(HE)及尼氏染色观察小鼠海马神经元病理变化,实时荧光定量PCR(RT-qPCR)法测定MEK1/2和ERK1/2的表达;蛋白免疫印迹法检测Bax、细胞色素(cCyt-c)、Cleaved Caspase3、Caspase3、MEK1/2、p-MEK、ERK1/2和p-ERK蛋白表达。结果:与对照组相比,DM高剂量组逃避潜伏期有显著性差异(P<0.05),DM中、高剂量组穿越平台次数均显著减少(P<0.05)。HE染色和尼氏染色显示,与对照组相比,DM各剂量组海马神经元出现变性坏死,尼氏小体减少。与对照组相比,DM各剂量组Bax、Cyt-c和ClCaspase3/Caspase3蛋白表达水平显著升高(P<0.05);DM高剂量组MEK1和ERK2 mRNA表达量明显升高,DM中、高剂量组MEK2和ERK1 mRNA表达量明显降低(均P<0.05);DM中、高剂量组p-MEK/MEK1/2蛋白表达比值增加,DM高剂量组pERK/ERK1/2蛋白表达比值减小(均P<0.05)。结论:DM经口短期暴露可致小鼠神经行为异常,海马神经元损伤诱导细胞凋亡,其机制可能与MEK/ERK信号通路异常激活有关。Objective:To investigate the potential role and molecular mechanisms of the MEK/ERK signaling pathway and apoptosis in the neurotoxicity induced by short-term exposure to deltamethrin(DM).Methods:Forty adult male C57BL/6J mice were randomly divided into control group,low-dose DM group(4.5 mg/kg),medium-dose DM group(9.0 mg/kg),and high-dose DM group(18.0 mg/kg).The mice were intragastrically administered for 30 days consecutively,and the control group was administered an equivalent volume of corn oil.Learning and memory abilities of mice were assessed using the Morris water maze(MWM).The pathological changes of hippocampal neurons in the mice were observed through hematoxylin and eosin(HE)staining and Nissl staining.The expression of MEK1/2 and ERK1/2 was detected by reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and the protein expression of Bax,cytochrome c(Cyt-c),Cleaved Caspase3,Caspase3,MEK1/2,p-MEK,ERK1/2,and p-ERK were detected by western blotting.Results:The high-dose DM group showed a significantly different escape latency period compared to the control group(P<0.05),while both the medium-and high-dose DM groups exhibited significantly reduced platform crossing times(P<0.05).HE and Nissl staining revealed degeneration,necrosis,and a reduction in Nissl bodies in hippocampal neurons across all DM doses groups compared to the control group.The protein expression levels of Bax,Cyt-c,and Cl Caspase3/Caspase3 were significantly elevated in the DM dose groups compared to the control group(P<0.05).The mRNA expression levels of MEK1 and ERK2 were significantly up-regulated in the high-dose DM group compared to the control group,whereas the mRNA expression levels of MEK2 and ERK1 were significantly downregulated in the medium-and high-dose DM groups(all P<0.05).In terms of protein expression,p-MEK/MEK1/2 expression was increased in the medium-and high-dose DM groups,while p-ERK/ERK1/2 expression was decreased in the high-dose DM group(P<0.05).Conclusion:Short-term oral exposure to DM can ind

关 键 词：溴氰菊酯 神经毒性 学习记忆能力 凋亡 MEK/ERK 

分 类 号：R749.12[医药卫生—神经病学与精神病学]