孕期阿奇霉素暴露对胎鼠肝脏发育和功能的影响及其特征

卢正杰; 毛彤芸; 刘可欣; 汪晖

doi:10.14188/j.1671-8852.2024.0595

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孕期阿奇霉素暴露对胎鼠肝脏发育和功能的影响及其特征

基础医学研究 | 更新时间：2026-11-05

- 孕期阿奇霉素暴露对胎鼠肝脏发育和功能的影响及其特征
- Effects of prenatal azithromycin exposure on fetal mouse liver development and function and the characteristics
- 武汉大学学报（医学版） 2025年46卷第9期页码：1097-1105
- 作者机构：
  
  1.武汉大学中南医院药学部湖北武汉 430071
  2.武汉大学基础医学院药理系湖北武汉 430071
  3.武汉大学中南医院关节与运动医学科湖北武汉 430071
  4.发育源性疾病湖北省重点实验室湖北武汉 430071
- 作者简介：
  
  卢正杰，男，1998—，医学博士生，主要从事药物发育毒理研究， E⁃mail: zhengjielu1998@163.com
  刘可欣，女，1996—，医学博士，副研究员，主要从事药物发育毒理研究， E⁃mail: Kathiehubu@163.com
  汪晖，女，1963—，医学博士，二级教授，博士生导师，主要从事药物发育毒理研究， E⁃mail: wanghui19@whu.edu.cn
- 基金信息：
  
  国家重点研发计划重点专项(2020YFA0803900);国家自然科学基金资助项目(32300973);中央高校基本科研业务费专项资金(2042023kf0066);武汉大学中南医院科技创新培育基金(CXPY2024014)
- DOI：10.14188/j.1671-8852.2024.0595
  中图分类号： R3
- 收稿：2024-08-08，
  
  纸质出版：2025-09-26
- 稿件说明：
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卢正杰,毛彤芸,刘可欣等.孕期阿奇霉素暴露对胎鼠肝脏发育和功能的影响及其特征[J].武汉大学学报（医学版）,2025,46(09):1097-1105.

LU Zhengjie,MAO Tongyun,LIU Kexin,et al.Effects of prenatal azithromycin exposure on fetal mouse liver development and function and the characteristics[J].Medical Journal of Wuhan University,2025,46(09):1097-1105.
卢正杰,毛彤芸,刘可欣等.孕期阿奇霉素暴露对胎鼠肝脏发育和功能的影响及其特征[J].武汉大学学报（医学版）,2025,46(09):1097-1105. DOI： 10.14188/j.1671-8852.2024.0595.

LU Zhengjie,MAO Tongyun,LIU Kexin,et al.Effects of prenatal azithromycin exposure on fetal mouse liver development and function and the characteristics[J].Medical Journal of Wuhan University,2025,46(09):1097-1105. DOI： 10.14188/j.1671-8852.2024.0595.

摘要

目的

探究不同时期、疗程和剂量的孕期阿奇霉素暴露(PAzE)对胎肝发育和功能的影响。

方法

孕鼠灌胃给予不同时期(孕中、晚期)、疗程(单疗程或多疗程)和剂量(50或200 mg·kg

-1

·d

-1

) PAzE，检测胎肝质量以及增殖、分化、凋亡和糖脂代谢功能基因表达。

结果

在雌性，PAzE抑制胎鼠肝脏增殖和分化相关基因表达，并促进凋亡相关基因表达。在雄性，PAzE主要促进胎鼠肝脏增殖和分化相关基因的表达，对凋亡无显著影响。进一步，PAzE抑制雌、雄胎鼠肝脏的糖异生功能，增强其甘油三酯、胆固醇和胆汁酸合成功能。此外，PAzE促进雌性胎鼠肝脏雌激素受体表达，并抑制雄性胎鼠雄激素受体表达。上述改变在孕晚期、多疗程和高剂量下更显著。

结论

PAzE可以性别差异性地影响胎肝发育，抑制雌、雄胎鼠肝脏的糖异生功能，增强其脂质合成功能，上述改变具有时期、疗程和剂量差异。

Abstract

Objective

To investigate the effects of prenatal azithromycin exposure (PAzE) on fetal mouse liver development and function at different stages

courses

and doses.

Methods

Pregnant mice were exposed to azithromycin during pregnancy at different stages (middle/late pregnancy)

courses (single course/multiple courses)

and doses (50 or 200 mg·kg

-1

·d

-1

) by intragastric administration. Fetal liver weight and mRNA expression of genes related to proliferation

differentiation

apoptosis

and glucose and lipid metabolism were detected.

Results

In female mice

PAzE inhibited the expression of genes related to liver proliferation and differentiation

and promoted the expression of genes related to apoptosis. In male mice

PAzE mainly promoted the expression of genes related to liver proliferation and differentiation

but exerted no significant effect on apoptosis. Furthermore

PAzE inhibited gluconeogenesis and enhanced the synthesis of triglyceride

cholesterol

and bile acid in the liver of female and male fetal mice. In addition

PAzE promoted the expression of estrogen receptor in the liver of female fetal mice and inhibited the expression of androgen receptor in male fetal mice. These changes were more significant in late pregnancy

with multiple courses and high doses.

Conclusion

PAzE could exert sex⁃specific effects on fetal liver development

inhibit gluconeogenesis in the liver of female and male fetal mice

and enhance their lipid synthesis function. These effects differ based on stages

courses

and doses.

关键词

Keywords

references

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