巨细胞对万科胺素敏感性的时间依赖差异是万科胺素诱导的急性损伤的基础
Yuya Yoshida1, Taiki Fukuda1, Kohei Fukuoka1
1Departments of Clinical Pharmacokinetics (Y.Y., T.F., T.N., T.T., N.N., K.O., Y.T., K.H., N.M.), Pharmaceutics (K.F., K.O., S.O.), Glocal Healthcare Science (A.T., S.K.), and Drug Discovery Structural Biology (K.M.), Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
The Journal of pharmacology and experimental therapeutics
|December 5, 2023
概括
范科米辛 (VCM) 诱导的损伤风险取决于服用时间. 巨细胞活动受到VCM时间的影响,驱动了这种差异,建议针对急性损伤 (AKI) 预防的向治疗.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 药理学 药理学是指药理学的学科.
- 免疫学 免疫学 免疫学
背景情况:
- 范科米辛 (VCM) 对于治疗耐药性感染至关重要,但经常导致急性损伤 (AKI).
- 目前的管理依赖于药物停用,强调了预防策略的必要性.
- 了解VCM对损伤的时间依赖性影响至关重要.
研究的目的:
- 在小鼠模型中,研究科米辛的施用时间对急性损伤诱导的影响.
- 阐明细胞在万科米辛诱导的毒性中所起的作用.
- 探索潜在的依赖时间的治疗干预措施,以预防香胺诱导的AKI.
主要方法:
- 使用1/2切除的小鼠来模拟损伤.
- 在不同的昼夜时间点 (ZT2和ZT14) 服用万科米辛.
- 评估了木素积累,AKI标记物,基因表达和巨细胞活动.
主要成果:
- 只有在轻期 (ZT2) 服用时,才观察到万科素诱导的AKI标志物,尽管药物积累类似.
- 基因组分析揭示了对单细胞和巨细胞活动的时间依赖性影响,包括脏巨细胞的丰富性和IL-1β表达.
- 使用克洛德罗纳酸废除的米素诱导IL-1β和AKI标志物表达在ZT2.2的巨细胞枯竭.
结论:
- 范科米辛的服用时间显著影响急性损伤的风险.
- 脏巨细胞在万科米的时间依赖性毒性中发挥着关键作用.
- 时间依赖的药理动力学和针对巨细胞的疗法对预防米诱导的AKI有很大的希望.
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