通过鼻内钒暴露建立啮齿动物嗅觉功能障碍模型

文献信息

中文摘要

嗅觉功能障碍日益被认为是暴露于环境毒物的重要后果，这是由于嗅觉系统的解剖和功能特征使吸入的毒物能够经由嗅觉通路到达中枢神经系统。实验性啮齿动物模型为在受控条件下研究毒物诱导的嗅觉损伤机制提供了有价值的工具。特别是，鼻内钒暴露已成为一种相关的实验方法，因为它再现了一种与环境相关的暴露途径，同时在整个嗅觉系统中诱导病理改变。本综述整合了来自鼻内钒暴露实验性啮齿动物模型的当前知识，涵盖嗅觉系统的解剖学和生理学、鼻内递送策略、钒诱导损伤的细胞和分子机制，以及相关的组织病理学、生化、行为和功能改变。钒诱导的损伤以氧化应激、线粒体功能障碍、神经炎症、细胞内信号通路失调和神经元变性为特征，导致整个嗅觉通路的结构和功能改变。最后，本综述指出了当前关于毒性损伤后嗅觉上皮再生和功能恢复的知识空白，并强调了未来研究的优先事项，以改进环境诱导嗅觉功能障碍的实验模型。

英文摘要

Olfactory dysfunction is increasingly recognized as an important consequence of exposure to environmental toxicants, owing to the anatomical and functional characteristics of the olfactory system, which allow inhaled toxicants to reach the central nervous system via the olfactory pathway. Experimental rodent models provide valuable tools for investigating the mechanisms underlying toxicant-induced olfactory injury under controlled conditions. In particular, intranasal vanadium exposure has emerged as a relevant experimental approach because it reproduces an environmentally relevant route of exposure while inducing pathological changes throughout the olfactory system. This review integrates current knowledge derived from experimental rodent models of intranasal vanadium exposure, covering the anatomy and physiology of the olfactory system, intranasal delivery strategies, the cellular and molecular mechanisms underlying vanadium-induced injury, and the associated histopathological, biochemical, behavioural and functional alterations. Vanadium-induced injury is characterized by oxidative stress, mitochondrial dysfunction, neuroinflammation, dysregulation of intracellular signalling pathways, and neuronal degeneration, leading to structural and functional alterations throughout the olfactory pathway. Finally, the review identifies current knowledge gaps regarding olfactory epithelial regeneration and functional recovery following toxic injury and highlights priorities for future research to improve experimental models of environmentally induced olfactory dysfunction.