Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
Department of Vascular and Thyroid Surgery, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
Exp Lung Res. 2022 Apr-Aug;48(4-6):168-177. doi: 10.1080/01902148.2022.2104409. Epub 2022 Aug 2.
Low tidal volume ventilation (LTVV) is a well-known ventilation mode which can improve ventilator-induced lung injury (VILI). However, the mechanism of LTVV ameliorating VILI has not yet been elucidated. In this study, we aimed to reveal LTVV protected against VILI by inhibiting the activation of the NLRP3 inflammasome in bronchoalveolar lavage fluid (BALF) from humans and lungs from mice.
Twenty-eight patients scheduled for video-assisted thoracoscopic esophagectomy were randomized to receive high-tidal-volume ventilation [ = 10 mL/kg without positive end-expiratory pressure (PEEP)] or LTVV ( = 5 mL/kg along with 5 cm of HO PEEP) during one-lung ventilation. BALF was collected before and at the end of surgery. Male C57BL/6 mice received high-tidal-volume ventilation, LTVV or MCC950 (an inhibitor of NLRP3). The activation of the formation of NLRP3 inflammasome in BALF from patients and in lungs from mice were analyzed.
LTTV decreased the peak airway pressure (), plateau airway pressure () and driving pressure (Δ) during one-lung ventilation. Additionally, LTVV not only inhibited pulmonary infiltration and inflammation caused by mechanical ventilation, but also suppressed the NLRP3 inflammasome activation in BALF from humans. In mice, ventilator-induced inflammatory response and pulmonary edema were suppressed by LTVV with an efficacy comparable to that of MCC950 treatment. Furthermore, LTVV, similar to MCC950, clearly decreased ventilator-induced NLRP3 inflammasome activation.
Our study showed that LTVV played a protective role in ventilator-induced lung injury by suppressing the activation of the NLRP3 inflammasome.
This study was registered in The Chinese Clinical Trial Registry, ChiCTR1900026190 on 25 September 2019.
低潮气量通气（LTVV）是一种众所周知的通气模式，可改善呼吸机相关性肺损伤（VILI）。然而，LTVV 改善 VILI 的机制尚未阐明。在这项研究中，我们旨在通过抑制支气管肺泡灌洗液（BALF）和小鼠肺中 NLRP3 炎性体的激活来揭示 LTVV 对 VILI 的保护作用。
28 名计划接受电视辅助胸腔镜食管切除术的患者随机分为高潮气量通气组（[=10ml/kg 无呼气末正压通气（PEEP）]或低潮气量通气组（[=5ml/kg 加 5cmH2O PEEP）]）在单肺通气期间。在手术前和手术结束时收集 BALF。雄性 C57BL/6 小鼠接受高潮气量通气、LTVV 或 MCC950（NLRP3 抑制剂）。分析患者 BALF 和小鼠肺中 NLRP3 炎性体形成的激活情况。
LTVV 降低了单肺通气期间的峰气道压（）、平台气道压（）和驱动压（Δ）。此外，LTVV 不仅抑制了机械通气引起的肺浸润和炎症，而且抑制了人类 BALF 中 NLRP3 炎性体的激活。在小鼠中，LTVV 与 MCC950 治疗一样，抑制了呼吸机诱导的炎症反应和肺水肿。此外，LTVV 与 MCC950 一样，明显降低了呼吸机诱导的 NLRP3 炎性体激活。
我们的研究表明，LTVV 通过抑制 NLRP3 炎性体的激活在呼吸机相关性肺损伤中发挥保护作用。
本研究于 2019 年 9 月 25 日在中国临床试验注册中心注册，注册号为 ChiCTR1900026190。
