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分析不同年龄和性别的小鼠胆汁中的胆汁酸成分。

Profiling bile acid composition in bile from mice of different ages and sexes.

作者信息

Liu Jiajian, Zhao Qing, Qu Chun, Ge Kun, Li Yang, Jia Wei, Zhao Aihua

机构信息

Center for Translational Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Physiol. 2025 Sep 1;16:1626215. doi: 10.3389/fphys.2025.1626215. eCollection 2025.

DOI:10.3389/fphys.2025.1626215
PMID:40959121
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12433987/
Abstract

INTRODUCTION

Bile BA profiling is important for understanding the pathogenetic mechanisms underlying gallbladder and gastrointestinal diseases. Until now, bile BAs have been explored mainly in adult male mice. However, sex- and age-related variations in the bile BA composition of normal experimental mice remain poorly characterized.

METHODS

BAs in bile from healthy, age-and sex-matched mice (8-week-old and 60-week-old) were quantified using ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometer (UPLC-TQ-MS). The bile BA profiles were comprehensively compared across different ages and sexes, along with comparisons within the same sex at different ages.

RESULTS

Total BAs (TBAs) in female mice were higher than those in male mice at both ages, although total BAs and BA profiles were similar between the two ages. High concentrations of BAs contributed significantly to the observed sex differences at both ages. Notably, both high- and low-concentration BAs were regulated with increasing age in male mice, while only low-concentration BAs were modulated with age in female mice. A remarkable sex difference in total cholesterol (TC) was also observed, along with a significant negative association between TC and BA profiles.

CONCLUSION

The findings demonstrate that bile BA profiles differ markedly with both sex and physiological age in commonly used normal laboratory mice, suggesting the need to consider for physiological differences related to sex and age when selecting suitable animals for pharmaceutical research and for mechanistic studies.

摘要

引言

胆汁酸(BA)谱分析对于理解胆囊和胃肠道疾病的发病机制很重要。到目前为止,胆汁酸主要在成年雄性小鼠中进行研究。然而,正常实验小鼠胆汁酸组成中与性别和年龄相关的差异仍未得到充分表征。

方法

使用超高效液相色谱-串联四极杆质谱仪(UPLC-TQ-MS)对健康、年龄和性别匹配的小鼠(8周龄和60周龄)胆汁中的胆汁酸进行定量。全面比较了不同年龄和性别的胆汁酸谱,以及同性别不同年龄之间的比较。

结果

在两个年龄段,雌性小鼠的总胆汁酸(TBA)均高于雄性小鼠,尽管两个年龄段的总胆汁酸和胆汁酸谱相似。高浓度胆汁酸在两个年龄段均对观察到的性别差异有显著贡献。值得注意的是,在雄性小鼠中,高浓度和低浓度胆汁酸均随年龄增长而受到调节,而在雌性小鼠中,只有低浓度胆汁酸随年龄变化。还观察到总胆固醇(TC)存在显著的性别差异,并且TC与胆汁酸谱之间存在显著的负相关。

结论

研究结果表明,在常用的正常实验室小鼠中,胆汁酸谱随性别和生理年龄有显著差异,这表明在为药物研究和机制研究选择合适的动物时,需要考虑与性别和年龄相关的生理差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479a/12433987/f0f273d7fa4c/fphys-16-1626215-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479a/12433987/1d6d0770087e/fphys-16-1626215-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479a/12433987/8ec5071d91b6/fphys-16-1626215-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479a/12433987/a25e7439fd2e/fphys-16-1626215-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479a/12433987/cef9141def0b/fphys-16-1626215-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479a/12433987/f0f273d7fa4c/fphys-16-1626215-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479a/12433987/1d6d0770087e/fphys-16-1626215-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479a/12433987/8ec5071d91b6/fphys-16-1626215-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479a/12433987/a25e7439fd2e/fphys-16-1626215-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479a/12433987/cef9141def0b/fphys-16-1626215-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/479a/12433987/f0f273d7fa4c/fphys-16-1626215-g005.jpg

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本文引用的文献

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Comparative profiling of serum, urine, and feces bile acids in humans, rats, and mice.比较人、大鼠和小鼠血清、尿液和粪便胆汁酸谱。
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Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance.
肠 FGF15 调节胆汁酸和胆固醇代谢,但不调节葡萄糖和能量平衡。
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Bile acid metabolomics identifies chenodeoxycholic acid as a therapeutic agent for pancreatic necrosis.胆汁酸代谢组学鉴定出鹅去氧胆酸是治疗胰腺坏死的一种治疗剂。
Cell Rep Med. 2023 Dec 19;4(12):101304. doi: 10.1016/j.xcrm.2023.101304. Epub 2023 Nov 29.
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Hyodeoxycholic acid ameliorates nonalcoholic fatty liver disease by inhibiting RAN-mediated PPARα nucleus-cytoplasm shuttling.熊去氧胆酸通过抑制 RAN 介导的 PPARα 核质穿梭改善非酒精性脂肪性肝病。
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Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis.熊去氧胆酸通过调节肠-肝轴缓解非酒精性脂肪性肝病。
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Evaluating the potential of tauroursodeoxycholic acid as add-on therapy in amelioration of streptozotocin-induced diabetic kidney disease.评估牛磺熊去氧胆酸作为辅助治疗在改善链脲佐菌素诱导的糖尿病肾病中的潜力。
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