生命早期低剂量镉暴露对阿尔茨海默病模型小鼠肝脏功能及脂质代谢的影响

doi:10.3969/j.issn.1004-616x.2026.02.001

癌变·畸变·突变 ›› 2026, Vol. 38 ›› Issue (2): 85-92.doi: 10.3969/j.issn.1004-616x.2026.02.001

• 论著 •

生命早期低剂量镉暴露对阿尔茨海默病模型小鼠肝脏功能及脂质代谢的影响

钟婧怡¹, 谢易容¹, 皮姝荣¹, 陈福彬¹, 丁树仁¹, 顾倩¹, 杨淋清², 何云¹

1. 中山大学公共卫生学院毒理学教研室, 广东广州 510080;
2. 深圳市疾病预防控制中心营养与食品安全所, 广东深圳 518055

收稿日期:2025-11-04 修回日期:2025-12-04 发布日期:2026-04-09
通讯作者: 杨淋清, 何云
作者简介:钟婧怡,E-mail:zhongjingyi18@163.com;谢易容,E-mail:lingxiu.xie.study@gmail.com。
基金资助:
国家自然科学基金(81472998,81872661)

Effect of early life low-dose cadmium exposure on liver function and lipid metabolism in a mouse model for Alzheimer's disease

ZHONG Jingyi¹, XIE Yirong¹, PI Shurong¹, CHEN Fubin¹, DING Shuren¹, GU Qian¹, YANG Linqing², HE Yun¹

1. Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou 510080;
2. Institute of Nutrition and Food Safety, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, Guangdong, China

Received:2025-11-04 Revised:2025-12-04 Published:2026-04-09

摘要/Abstract

摘要： 目的： 研究生命早期低剂量镉暴露对阿尔茨海默病(AD)模型小鼠肝脏功能和脂质代谢的影响。方法： AD小鼠和野生型(WT)小鼠母鼠自孕前1周起通过饮水镉染毒(0、1、10 mg/L)至F1代小鼠6月龄，在F1代小鼠1、3、6月龄时采集小鼠血液检测血脂和肝功能指标，并采集肝脏组织通过逆转录实时荧光定量PCR法(RT-qPCR)测定金属硫蛋白MT1和MT2的mRNA表达水平。结果： 与3月龄染毒WT小鼠相比，同龄同剂量AD小鼠体质量、肝质量、肝系数、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)和丙氨酸氨基转移酶(ALT)浓度显著增加(P<0.05)，低密度脂蛋白(LDL)、动脉硬化指数(AI)和肝脏MT1 mRNA表达降低(P<0.05)。与6月龄染毒组WT小鼠相比，同龄同剂量AD小鼠体质量、肝质量、TC、TG、HDL升高(P<0.05)，天门冬氨酸氨基转移酶(AST)和AST/ALT降低(P<0.05)。镉和APP/PS1基因型对小鼠体质量、肝质量、TC、LDL和TG/HDL存在交互作用(P<0.05)。结论： 生命早期低剂量镉暴露可诱导AD小鼠血脂紊乱和肝功能异常，并且在环境镉暴露水平(1 mg/L)即可降低MT1和MT2表达。

关键词: 镉, 阿尔茨海默病, 血脂, 肝功能, 金属硫蛋白

Abstract: OBJECTIVE: To investigate effect of low-dose cadmium exposure in early life on liver function and lipid metabolism in a mouse model for Alzheimer's disease(AD mice). METHODS: AD and wild-type(WT) mice were exposed to cadmium via drinking water(0,1,and 10 mg/L) from one week before pregnancy until 6 months of age. Blood samples were collected from F1 generation mice at the ages of 1,3,and 6 months,and serum lipid and liver function indices were measured. Liver tissues were collected,and mRNA expression levels of metallothionein 1(MT1) and metallothionein 2(MT2) in the livers were determined by quantitative real-time polymerase chain reaction(RT-qPCR). RESULTS: Compared with 3-month-old toxicant-exposed WT mice, age-and dose-matched AD mice showed increased body weight, liver weight,liver coefficient,TC,TG,HDL,and ALT(P<0.05),along with decreased LDL,AI,and hepatic MT1 mRNA expression(P<0.05). In comparison with 6-month-old toxicant-exposed WT mice,age-and dose-matched AD mice exhibited elevated body weight,liver weight,TC,TG,and HDL(P<0.05),along with decreased AST and AST/ALT ratio(P<0.05). Furthermore,interactive effects of cadmium and APP/PS1 genotype were observed on body weight, liver weight, TC, LDL, and TG/HDL ratio(P<0.05). CONCLUSION: Low-dose cadmium exposure in early life can induce dyslipidemia and abnormal liver function in AD mice,therefore exposure to environmental cadmium levels(1 mg/L) can reduce expression level of MT1 and MT2.

Key words: cadmium, Alzheimer's disease, serum lipids, liver function, metallothionein

中图分类号:

R114

钟婧怡, 谢易容, 皮姝荣, 陈福彬, 丁树仁, 顾倩, 杨淋清, 何云. 生命早期低剂量镉暴露对阿尔茨海默病模型小鼠肝脏功能及脂质代谢的影响[J]. 癌变·畸变·突变, 2026, 38(2): 85-92.

ZHONG Jingyi, XIE Yirong, PI Shurong, CHEN Fubin, DING Shuren, GU Qian, YANG Linqing, HE Yun. Effect of early life low-dose cadmium exposure on liver function and lipid metabolism in a mouse model for Alzheimer's disease[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2026, 38(2): 85-92.

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生命早期低剂量镉暴露对阿尔茨海默病模型小鼠肝脏功能及脂质代谢的影响

Effect of early life low-dose cadmium exposure on liver function and lipid metabolism in a mouse model for Alzheimer's disease

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