辛提利马布与乙氨基结合,通过亡和乱的胆酸通路加剧肝损伤
Jianing Qin1, Bin Yu2, Yuanyuan Zhou2
1The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, PR China; Liuzhou People's Hospital, Liuzhou 545000, PR China.
Toxicology
|March 1, 2025
概括
将辛蒂利马布与乙氨基 (APAP) 结合使用,可显著恶化小鼠肝损伤. 这种药物组合增加了氧化应激,亡,并破坏了胆酸代谢,凸显了同时服用的风险.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
背景情况:
- 辛提利马布 (免疫检查点抑制剂) 和乙氨基 (APAP) 与肝损伤有关.
- 辛蒂利马布和APAP的联合肝毒性作用尚不清楚.
研究的目的:
- 在小鼠模型中研究联合辛蒂利马布和APAP对肝损伤的恶化作用.
- 探索亡和胆酸破坏在这种联合肝毒性中的作用.
主要方法:
- 小鼠接受了sintilimab和APAP的单独或组合治疗.
- 评估了血清肝酶,组织学损伤,氧化应激标志物,亡标志物和胆酸概况.
- 测量了CYP7A1基因表达.
主要成果:
- 组合疗法显著提高肝酶,并诱导组织学损伤.
- 同时治疗增加了氧化应激和亡标志物 (细胞染色体C,卡斯帕斯,巴克斯).
- 观察到CYP7A1的下调和胆酸代谢的改变 (初级降低,二级增加).
结论:
- 辛提利马布通过增加氧化应激和亡来加剧APAP诱导的肝损伤.
- 胆酸平衡的破坏有助于肝毒性恶化.
- 建议在与sintilimab和APAP同时使用时谨慎和监测.
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