肠肝微生理系统揭示了潜在的交叉声机制,调节药物代谢
Dhimas Agung Kurniawan1, Sylvia Leo2, Mutsumi Inamatsu3
1Department of Chemical System Engineering, Graduate School of Engineering, University of Tokyo, Tokyo 113-8656, Japan.
PNAS nexus
|February 22, 2024
概括
研究人员使用微生理系统探索了肝脏和小肠细胞之间的交叉声. 他们发现,由肝细胞释放的脂肪酸,如酸,可以增强肝脏中药物代谢.
科学领域:
- 药理学 药理学是指药理学的学科.
- 肝病学 肝病学是一种肝病学.
- 胃肠病学 胃肠病学
背景情况:
- 肝脏和小肠是口服药物代谢的关键.
- 肠肝循环表明交叉声会影响药物代谢,但机制尚不清楚.
- 共同培养肝脏和肠道细胞可以促进药物代谢.
研究的目的:
- 阐明人类初级肝细胞 (PXB细胞) 和诱导多能干细胞 (iPSC) 衍生的肠细胞之间的交叉机制.
- 研究微生理系统 (MPS) 在模拟这种相互作用中的作用.
- 确定影响药物代谢的交叉通话中涉及的特定因素.
主要方法:
- 在微生理系统 (MPS) 内的PXB细胞和iPSC衍生的肠细胞与 perfusion 和直接氧化一起培养.
- 评估PXB细胞功能 (白蛋白分泌,细胞染色体P450 (CYP) 活性) 和肠细胞屏障完整性.
- 利用RNA测序来分析PXB细胞中的基因表达变化.
主要成果:
- MPS成功地增强了PXB细胞白蛋白分泌和CYP活性,同时保持了肠道细胞屏障的完整性.
- RNA测序揭示了PXB细胞中脂肪酸代谢途径的显著上调.
- 阿拉基酸被确定为增强CYP酶活性的一种因素,模仿培养效应.
结论:
- 建议使用一种涉及胆汁酸,脂蛋白和脂肪酸 (如酸) 的交叉机制来增强肝脏药物代谢.
- 该MPS是研究肝肠相互作用及其对药物代谢的影响的合适平台.
- 了解这种交叉对预测口服药物的药理动力学和疗效至关重要.
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