抑制YAP可下调NLRP3炎性体,改善抗结核药物性肝损伤。

IF 1.2 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Xenobiotica Pub Date : 2025-02-01 Epub Date: 2025-05-04 DOI:10.1080/00498254.2025.2497050
Yifei Long, Xueying Li, Yue Liu, Mi Zhang, Fumin Feng
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引用次数: 0

摘要

yes相关蛋白(YAP)是Hippo信号通路的核心效应分子,但其在抗结核药物性肝损伤(ADLI)中的作用尚不清楚。我们旨在探讨YAP对ADLI中NLRP3炎性体的调节作用及其潜在的肝保护作用。建立ADLI动物模型。分别于0、7、14、21 d检测实验动物各项指标。第7天,HE染色观察肝组织,肝脏指数、ALT和AST水平证实ADLI模型。检测YAP mRNA和蛋白水平,观察YAP抑制剂的作用,分析NLRP3炎症小体、炎症和氧化应激指标。结果发现,在ADLI过程中,YAP mRNA和蛋白水平先升高后降低,这是由于YAP抑制剂的作用。YAP引起NLRP3炎性体指标升高,炎症和氧化应激表达增加。饲喂YAP抑制剂后,这些指标降低。结果提示,靶向YAP可能是减轻抗结核药物性肝损伤的一种新的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inhibition of YAP can down-regulate NLRP3 inflammasome and improve anti-tuberculosis drug-induced liver injury.

Yes-associated protein (YAP) is a core effector molecule in the Hippo signalling pathway, but its role in antituberculosis drug-induced liver injury (ADLI) is unclear. We aimed to explore the regulatory effects of YAP on the NLRP3 inflammasome in ADLI and its potential hepatoprotective effects.An ADLI animal model was established. Various indicators of experimental animals were detected at 0, 7, 14, and 21 days. On day 7, HE staining observed liver tissue, and liver index, ALT, and AST levels confirmed the ADLI model. YAP's mRNA and protein levels were examined, YAP inhibitor effects were observed, and NLRP3 inflammasome, inflammation, and oxidative stress indicators were analysed.It was found that the mRNA and protein levels of YAP increased during ADLI and then decreased due to the action of YAP inhibitors. YAP caused an elevation in NLRP3 inflammasome indicators, as well as increased expression of inflammation and oxidative stress. After feeding with YAP inhibitors, these indicators were reduced.The results suggest that targeting YAP may be a novel therapeutic strategy for alleviating antituberculosis drug-induced liver injury.

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来源期刊
Xenobiotica
Xenobiotica 医学-毒理学
CiteScore
3.80
自引率
5.60%
发文量
96
审稿时长
2 months
期刊介绍: Xenobiotica covers seven main areas, including:General Xenobiochemistry, including in vitro studies concerned with the metabolism, disposition and excretion of drugs, and other xenobiotics, as well as the structure, function and regulation of associated enzymesClinical Pharmacokinetics and Metabolism, covering the pharmacokinetics and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in manAnimal Pharmacokinetics and Metabolism, covering the pharmacokinetics, and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in animalsPharmacogenetics, defined as the identification and functional characterisation of polymorphic genes that encode xenobiotic metabolising enzymes and transporters that may result in altered enzymatic, cellular and clinical responses to xenobioticsMolecular Toxicology, concerning the mechanisms of toxicity and the study of toxicology of xenobiotics at the molecular levelXenobiotic Transporters, concerned with all aspects of the carrier proteins involved in the movement of xenobiotics into and out of cells, and their impact on pharmacokinetic behaviour in animals and manTopics in Xenobiochemistry, in the form of reviews and commentaries are primarily intended to be a critical analysis of the issue, wherein the author offers opinions on the relevance of data or of a particular experimental approach or methodology
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