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伏里可纳的代谢特征 - - 在大鼠中诱导肝损伤

Qian Du¹, Mengmeng Teng¹, Luting Yang¹

¹Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, China.

Chemico-biological interactions

|September 2, 2023

概括

在老鼠中,沃里可纳诱导的肝损伤显示了脂质代谢的改变和酸丁胆的减少. 这些代谢变化可以作为早期指标,并揭示肝损伤的机制.

科学领域:

药理学药理学是指药理学的学科.
毒理学毒理学毒理学
代谢学代谢学代谢学

背景情况:

沃里康纳 (VOR) 是一种广泛使用的抗真菌药物.
VOR诱导的肝损伤 (VILI) 是一种具有严重临床后果的显著不良影响.
了解VILI的代谢概况和机制对于患者的安全至关重要.

研究的目的:

在VOR诱导的肝损伤的小鼠模型中研究血代谢特征的变化.
为了确定潜在的生物标志物用于早期检测VILI.
阐明VILI的潜在机制,重点关注脂质代谢.

主要方法:

采用非向代谢学来分析从VOR治疗的老鼠的血样本.
相关性分析将改变的代谢物与肝功能指数 (ALT,AST) 联系起来.
接收器操作特征 (ROC) 曲线分析和病理评分被用于选生物标志物. 评估了与脂质代谢相关的基因表达.

主要成果:

VOR诱导的肝损伤的特征是ALT/AST升高,肝脂滴,炎症和纤维化.
超过50%的显著改变的血代谢物是脂质,包括改变的胆固醇和胆酸代谢物.
观察到酸丁胆 (PC) 的降低,可能表明VILI. 建议减少脂肪酸氧化和胆酸分泌作为机制.

结论:

血代谢分析显示,在VOR诱导的肝损伤期间,脂质代谢发生了显著的改变.
酸丁胆的降低可能作为VILI的预测生物标志物.
脂肪酸氧化和胆酸分泌的损害是导致VILI的潜在机制.

关键词:

胆酸是什么意思胆酸是什么意思生物标志物生物标志物药物诱导的肝损伤是药物诱导的肝损伤.脂质新陈代谢脂质新陈代谢代谢学代谢学代谢学沃里康纳 (Voriconazole) 是一种可以

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