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内分泌干扰剂温克洛林通过ENOS/Nox4/IRE1α信号传递引起内皮损伤

Erika Esposito¹, Chiara Indolfi², Ivana Bello¹

¹Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Via D. Montesano 49, 80131, Naples, Italy.

European journal of pharmacology

|June 20, 2024

概括

芬克洛佐林真菌杀菌剂通过氧化应激破坏内皮功能,导致血管损伤. 它损害了氧化信号传输,并引发了内质网膜应激,可能导致心血管疾病.

科学领域:

毒理学毒理学毒理学
内分泌学在内分泌学.
心血管生物学心血管生物学

背景情况:

文克洛佐林 (VCZ) 是一种被广泛使用的二氧化物杀菌剂,具有已知的内分泌干扰特性.
虽然VCZ对各种器官的影响已被记录,但其对血管功能的影响仍未得到解决.
鉴于其在心血管病理中的潜在作用,了解VCZ的血管作用至关重要.

研究的目的:

调查克洛佐林诱导的血管损伤背后的潜在机制.
评估VCZ对大动脉内皮和光滑肌组成部分的影响.
阐明参与VCZ介导的内皮功能障碍的信号通路.

主要方法:

在暴露于VCZ的小鼠大动脉中评估血管功能 (放松和收缩).
在内皮细胞中对内皮氧化合成酶 (eNOS) /氧化 (NO) 信号的分析.
评估反应性氧物种 (ROS) 生成,氧化应激标志物和内分泌网膜 (ER) 应激指标 (IRE1α酸化).

主要成果:

短暂的VCZ暴露通过破坏eNOS/NO信号和促进eNOS脱,增加酸铁氨酸和ROS,损害了内皮功能.
长时间暴露于VCZ导致通过Nox4上调调节增加ROS产量,增加马隆迪化物,并降低了NO水平.
由VCZ诱导的氧化应激和内皮功能障碍与ER应激有关,IRE1α酸化证明了这一点.

结论:

VCZ通过一种涉及eNOS/Nox4/IRE1α轴的氧化应激机制诱导内皮功能障碍.
急性VCZ暴露主要影响eNOS解,而慢性暴露涉及Nox4/IRE1α信号.
暴露于VCZ可能会导致与内皮功能障碍有关的心血管疾病的发展或进展.

关键词:

贝克 (BAEC) 是一个英语单词.脑内皮质 (Endothelium) 是一个内皮质.我们的老鼠是老鼠.第4号x4号氧化应激是一种氧化应激.温克洛佐林是一种温克洛佐林.

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