石房蛤毒素暴露对F1代小鼠认知功能的影响及其作用机制

doi:10.3969/j.issn.1004-616x.2026.01.005

癌变·畸变·突变 ›› 2026, Vol. 38 ›› Issue (1): 27-33.doi: 10.3969/j.issn.1004-616x.2026.01.005

• 论著 • 上一篇

石房蛤毒素暴露对F1代小鼠认知功能的影响及其作用机制

陈妹^1,2, 黄海燕², 林玲玲², 任晓虎², 陈效², 刘云岗¹, 刘建军^1,2

1. 南方医科大学公共卫生学院, 广东广州 510515;
2. 深圳市疾病预防控制中心, 深圳市现代毒理学重点实验室, 深圳市卫生毒理学医学重点学科, 广东深圳 518055

收稿日期:2025-07-28 修回日期:2025-09-29 发布日期:2026-01-30
通讯作者: 刘建军
基金资助:
深圳市基础研究学科布局项目(JCYJ20180508152311822)；深圳市医学重点学科建设经费资助项目(SZXK069)；深圳市医疗卫生三名工程项目(SZSM202211010)

Effect and mechanism of saxitoxin exposure on cognitive function in F1 generation mice

CHEN Mei^1,2, HUANG Haiyan², LIN Lingling², REN Xiaohu², CHEN Xiao², LIU Yungang¹, LIU Jianjun^1,2

1. School of Public Health, Southern Medical University, Guangzhou 510515;
2. Shenzhen Center for Disease Control and Prevention, Shenzhen Key Laboratory of Modern Toxicology, Shenzhen Medical Key Discipline of Health Toxicology, Shenzhen 518055, Guangdong, China

Received:2025-07-28 Revised:2025-09-29 Published:2026-01-30

摘要/Abstract

摘要： 目的：探究石房蛤毒素(STX)暴露对F1代小鼠认知功能的影响及其可能机制。方法：通过饮水染毒，在C57BL/6J小鼠亲代妊娠期和哺乳期至F1子代成年期期间进行STX染毒，剂量分别为0、0.02、0.20、2.00 μg/kg。对出生后第60天和第180天(PND60和PND180)的小鼠，分别采用Morris水迷宫实验评估其记忆及认知功能，NeuN免疫组织化学染色法评估小鼠皮层神经损伤情况，串联质量标签(TMT)定量蛋白质组学技术对小鼠皮层组织差异蛋白进行筛选及富集分析，并利用Western blot法对差异蛋白进行验证，试剂盒检测皮层组织ATP水平。结果：与对照组比较，STX各剂量组间母鼠体质量、饮水量以及F1子代小鼠的体质量增长均无明显差异(P>0.05)。与对照组相比，Morris水迷宫实验结果表明，STX染毒组PND180小鼠到达平台时间显著增加、穿越平台次数显著减少、目标象限活动时间占比显著减少(均为P<0.05)，而PND60阶段尚未观察到显著差异；免疫组织化学染色结果表明，STX染毒组PND180小鼠神经元数量显著减少(P<0.05)；蛋白质组学分析结果表明，2.00 μg/kg组PND60小鼠筛选出295个差异蛋白，PND180小鼠筛选出327个差异蛋白；PND60和PND180小鼠GO及KEGG分析均富集到氧化磷酸化途径。Western blot检测结果表明，与对照组相比，PND180小鼠皮层氧化磷酸化通路上的Ndufs1和Ndufb9蛋白表达水平显著升高(P<0.05)，PND60蛋白表达水平无显著差异(P>0.05)。试剂盒检测结果表明，STX染毒组PND180小鼠ATP水平较对照组显著降低(P<0.05)。结论：母鼠妊娠和哺乳期至子鼠成年期STX暴露致F1代小鼠认知损伤，其作用机制可能与氧化磷酸化途径有关。

关键词: 石房蛤毒素, 认知损伤, 蛋白质组学, 氧化磷酸化

Abstract: OBJECTIVE： To investigate effects of saxitoxin (STX) exposure on cognitive function in F1 generation mice and its underlying mechanisms. METHODS： C57BL/6J mice were exposed to STX via drinking water during gestation and lactation to adulthood at doses of 0.00， 0.02， 0.20， or 2.00 μg/kg. Cognitive and memory functions were assessed in postnatal day 60 (PND60) and PND180 mice using the Morris water maze test， cortical neurotoxicity was evaluated by NeuN immunohistochemical staining， differentially expressed proteins in cortical tissues were screened and analyzed via Tandem Mass Tag (TMT) quantitative proteomics and enrichment analysis， key proteins were validated by Western blot， and cortical ATP levels were measured with a commercial kit. RESULTS： At STX doses of 0.02，0.20，and 2.00 μg/kg， no significant differences in maternal body weight，water intake，or body weight gain of F1 generation mice compared with the control group (P>0.05). In the Morris water maze， PND180 offspring exposed to STX exhibited prolonged platform-finding latency， reduced platform crossings， and decreased target quadrant occupancy compared to the control group (all P<0.05)， while no differences were detected at PND60. Immunohistochemical analysis revealed significantly fewer cortical neurons in PND180 mice following STX exposure (P<0.05). Proteomic profiling identified 295 DEPs at PND60 and 327 DEPs at PND180 in the 2.00 μg/kg group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted oxidative phosphorylation (OXPHOS) as a critical pathway in both age groups. Western blot confirmed elevated expression of OXPHOS-related proteins Ndufs1 and Ndufb9 in PND180 cortical tissues (P<0.05)， with no significant changes at PND60. Cortical ATP levels were also significantly reduced in STX-exposed PND180 mice (P<0.05). CONCLUSION： STX exposure from gestation and lactation to adulthood induces cognitive impairment in F1 generation mice，and its mechanism of action may involve the oxidative phosphorylation pathway.

Key words: saxitoxin, cognitive impairment, proteomics, oxidative phosphorylation

中图分类号:

R996.3

陈妹, 黄海燕, 林玲玲, 任晓虎, 陈效, 刘云岗, 刘建军. 石房蛤毒素暴露对F1代小鼠认知功能的影响及其作用机制[J]. 癌变·畸变·突变, 2026, 38(1): 27-33.

CHEN Mei, HUANG Haiyan, LIN Lingling, REN Xiaohu, CHEN Xiao, LIU Yungang, LIU Jianjun. Effect and mechanism of saxitoxin exposure on cognitive function in F1 generation mice[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2026, 38(1): 27-33.

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石房蛤毒素暴露对F1代小鼠认知功能的影响及其作用机制

Effect and mechanism of saxitoxin exposure on cognitive function in F1 generation mice

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