巨噬细胞在呼吸机引起的肺损伤（VILI）中被激活，并伴有巨噬细胞焦亡。瑞马唑仑 (Re) 具有抑制巨噬细胞活化的作用。在本研究中，我们旨在研究 VILI 中 Re 的机制。使用 C57BL/6 小鼠创建 VILI 模型（20 mL/kg 机械通气）。从支气管肺泡灌洗液（BALF）中分离肺泡巨噬细胞，并接受机械拉伸以模拟体外机械通气。 VILI模型小鼠用Re（16 mg/kg）处理，评估肺泡结构、湿/干（W/D）重量比、内皮屏障抗原（EBA）通透性指数、BALF蛋白含量、炎症因子、巨噬细胞焦亡、细胞焦亡使用一系列生物学实验研究相关因素和易位蛋白（TSPO）水平。通过拯救实验确定Re是否通过调节TSPO减轻巨噬细胞焦亡。Re减轻VILI，表现为VILI期间肺组织异常形态的改善，肺W/D重量比、肺EBA通透性指数和BALF蛋白含量的降低。通过下调炎症因子（髓过氧化物酶、丙二醛、8-羟基-2 脱氧鸟苷、白介素-6、肿瘤坏死因子-α、巨噬细胞炎症蛋白-2、白细胞介素-1β 和白细胞介素），重新减轻 VILI 期间的肺部炎症和巨噬细胞焦亡-18) 和细胞焦亡因子（裂解的gasdermin D (GSDMD)/GSDMD 值、NOD 样受体热蛋白结构域相关蛋白 3 (NLRP3) 和 caspase-1）。重新激活巨噬细胞中的 TSPO。 TSPO 过表达可挽救细胞拉伸抑制的巨噬细胞活力和细胞拉伸诱导的巨噬细胞焦亡。Re 通过激活 TSPO 抑制巨噬细胞焦亡来缓解 VILI。

Macrophages are activated in ventilator-induced lung injury (VILI), accompanied by macrophage pyroptosis. Remimazolam (Re) plays a role in inhibiting macrophage activation. In this study, we aimed to investigate the mechanism of Re in VILI.A VILI model (20 mL/kg mechanical ventilation) was created using C57BL/6 mice. Alveolar macrophages were isolated from bronchoalveolar lavage fluid (BALF) and received mechanical stretching to simulate the mechanical ventilation in vitro. VILI model mice were treated with Re (16 mg/kg) to assess the alveolar structure, wet/dry (W/D) weight ratio, endothelial barrier antigen (EBA) permeability index, BALF protein content, inflammatory factors, macrophage pyroptosis, pyroptosis-related factors, and translocator protein (TSPO) level using a series of biological experiments. Whether Re alleviated macrophage pyroptosis by regulating TSPO was determined by rescue experiments.Re alleviated VILI, as evidenced by improvement of abnormal morphology of lung tissues during VILI and decreases in the lung W/D weight ratio, lung EBA permeability index, and BALF protein content. Re attenuated pulmonary inflammation and macrophage pyroptosis during VILI via down-regulation of inflammatory factors (myeloperoxidase, malondialchehyche, 8-hydroxy-2 deoxyguanosine, interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2, interleukin-1β, and interleukin-18), and pyroptosis factors (cleaved gasdermin D (GSDMD)/GSDMD value, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and caspase-1). Re activated TSPO in macrophages. TSPO overexpression rescued the cell stretch-inhibited macrophage viability and cell stretch-induced macrophage pyroptosis.Re alleviates VILI by activating TSPO to inhibit macrophage pyroptosis.