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Updated: Jan 9, 2026

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集成的单细胞转录组学和蛋白组学阐明了 rifampicin 诱导的肝毒性的分子机制和解毒策略

Junhui Chen¹, Qian Zhang^1,2, Jingnan Huang^1,3

¹Department of Pulmonary and Critical Care Medicine, Shenzhen Institute of Respiratory Diseases, Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, China.

International journal of biological sciences

|December 9, 2025

概括

利芬素通过增加氧化应激和改变脂肪酸代谢而导致肝损伤. 罗斯马林酸在小鼠模型中有效地保护了这种药物诱导的肝毒性.

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:

利芬素对于结核病治疗至关重要,但会导致严重的肝毒性,往往导致治疗中止.
我们对利芬素诱导的肝损伤机制的了解有限,需要新的治疗策略.

研究的目的:

综合调查瑞芬素诱导的肝毒性细胞和分子机制.
为了确定潜在的治疗干预措施,以减轻利芬素诱导的肝损伤.

主要方法:

使用了一种由里芬素诱导的小鼠肝毒性模型.
综合的多组学方法:单细胞RNA测序,大量RNA测序,蛋白学和代谢学.
评估了罗斯马林酸 (RA) 的治疗效果.

主要成果:

鉴定了与高反应性氧物种 (ROS) 和活性脂肪酸氧化相关的特定区域的肝细胞损伤.
观察到PXR和Cyp3a11的上调,抗氧化基因的下调,以及改变的mTOR和脂肪酸氧化途径.
证明使用罗斯马林酸显著减轻了因利芬素引起的肝损伤.

结论:

里芬素诱导的肝毒性涉及复杂的细胞和分子变化,包括氧化应激和代谢重编程.
罗斯马林酸显示出作为一种潜在的治疗药物来治疗因利芬素引起的肝损伤的潜力.

关键词:

肝细胞肝细胞肝细胞氧化应激是一种氧化应激.有反应性氧物种的反应性氧物种.里法胺是一种药物.罗斯马林酸. 罗斯马林酸.

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