美国哈佛医学院Stephen D. Liberles团队发现气道关闭诱发的一种迷走神经反射。2024年3月6日，国际知名学术期刊《自然》在线发表了这一成果。

研究人员描述了气道关闭诱发的迷走神经神经元反射导致喘息的特征。体内迷走神经节成像显示，专门的感觉神经元能检测气道压缩，但不能检测气道伸展。表达PVALB的迷走神经元介导气道关闭反应，并支配称为神经上皮小体（NEB）的肺上皮细胞群。在没有气道威胁的情况下，刺激NEB或迷走神经PVALB神经元会诱发喘息，而去除NEB或迷走神经PVALB神经元则会消除气道闭合反应引起的喘息。

单细胞RNA测序显示NEB一致地表达机械感受器PIEZO2，在NEB中定向敲除Piezo2可消除对气道关闭的反应。NEB对Hering-Breuer吸气反射是不可或缺的，这表明离散的末端结构能检测气道关闭和充气。与梅克尔细胞参与触觉类似，NEB也是表达PIEZO2的上皮细胞，而且对肺机械感觉的一个方面至关重要。这些发现拓展了人们对气道神经元多样性的认识，并揭示了一条专门的迷走神经通路，该通路可检测气道关闭，从而帮助保护呼吸功能。

据介绍，在人的一生中，必须持续保持呼吸道的完整性。感觉神经元可防止气道阻塞，并每时每刻做出重要反射以维持呼吸功能。肺活量下降在许多呼吸系统疾病中都很常见，而且会危及生命，胸壁创伤、气胸或气道压迫都会急性诱发肺塌陷。

附：英文原文

Title: A vagal reflex evoked by airway closure

Author: Schappe, Michael S., Brinn, Philip A., Joshi, Narendra R., Greenberg, Rachel S., Min, Soohong, Alabi, AbdulRasheed A., Zhang, Chuchu, Liberles, Stephen D.

Issue&Volume: 2024-03-06

Abstract: Airway integrity must be continuously maintained throughout life. Sensory neurons guard against airway obstruction and, on a moment-by-moment basis, enact vital reflexes to maintain respiratory function1,2. Decreased lung capacity is common and life-threatening across many respiratory diseases, and lung collapse can be acutely evoked by chest wall trauma, pneumothorax or airway compression. Here we characterize a neuronal reflex of the vagus nerve evoked by airway closure that leads to gasping. In vivo vagal ganglion imaging revealed dedicated sensory neurons that detect airway compression but not airway stretch. Vagal neurons expressing PVALB mediate airway closure responses and innervate clusters of lung epithelial cells called neuroepithelial bodies (NEBs). Stimulating NEBs or vagal PVALB neurons evoked gasping in the absence of airway threats, whereas ablating NEBs or vagal PVALB neurons eliminated gasping in response to airway closure. Single-cell RNA sequencing revealed that NEBs uniformly express the mechanoreceptor PIEZO2, and targeted knockout of Piezo2 in NEBs eliminated responses to airway closure. NEBs were dispensable for the Hering–Breuer inspiratory reflex, which indicated that discrete terminal structures detect airway closure and inflation. Similar to the involvement of Merkel cells in touch sensation3,4, NEBs are PIEZO2-expressing epithelial cells and, moreover, are crucial for an aspect of lung mechanosensation. These findings expand our understanding of neuronal diversity in the airways and reveal a dedicated vagal pathway that detects airway closure to help preserve respiratory function.

DOI: 10.1038/s41586-024-07144-2

Source: https://www.nature.com/articles/s41586-024-07144-2