Liu Jiajian, Zhao Qing, Qu Chun, Ge Kun, Li Yang, Jia Wei, Zhao Aihua
Center for Translational Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Physiol. 2025 Sep 1;16:1626215. doi: 10.3389/fphys.2025.1626215. eCollection 2025.
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.
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.
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.
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.
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。
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。
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。
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。