急性肺损伤 (ALI) 是一种严重威胁健康的综合征，其肺部有强烈的炎症反应，进展会导致急性呼吸窘迫综合征 (ARDS)。大承气汤冲剂（DDG）具有肺保护作用，但其缓解ALI的潜在调节机制有待进一步挖掘。本研究旨在探讨DDG对脂多糖（LPS）诱导的ALI模型体内外的作用及潜在机制。采用LPS处理的Balb/c小鼠和BEAS-2B细胞分别构建体内和体外ALI模型。进行苏木精-伊红 (HE)、肺组织湿重/干重 (W/D) 计算以及 BALF 中的总蛋白和乳酸脱氢酶 (LDH) 测定，以评估肺组织损伤和肺水肿的程度。采用酶联免疫吸附法（ELISA）检测BALF、血清和血清中肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）和白细胞介素-18（IL-18）的水平。细胞上清液。采用 qRT-PCR 检测肺组织和 BEAS-2B 细胞中炎症因子、Z-DNA 结合蛋白 1 (ZBP1) 和受体相互作用蛋白激酶 1 (RIPK1) 的表达。采用免疫荧光双重染色和免疫共沉淀检测ZBP1和RIPK1的相对表达和共定位。采用Cell Counting Kit-8 (CCK-8)检测LPS和DDG对BEAS-2B细胞活性的影响。免疫印迹（WB）分析肺组织和BEAS-2B细胞中PANoptosis相关蛋白的表达。在体内，DDG预处理可以剂量依赖性地改善ALI小鼠肺组织的病理变化，并降低W/肺D比、总蛋白浓度、BALF中LDH含量。在体外，DDG 逆转了 LPS 对 BEAS-2B 细胞活力的抑制作用。同时，DDG显着降低体内外炎症因子水平。此外，DDG还可以抑制PANoptosis相关蛋白的表达水平，特别是上游关键调控分子ZBP1和RIPK1。DDG可以抑制过度炎症和PANoptosis，从而缓解LPS诱导的ALI，具有良好的抗炎和肺保护作用。 。该研究为DDG的进一步发展奠定了理论基础，并为靶向PANoptosis的ALI治疗提供了新前景。版权所有©2024。Elsevier B.V.出版。

Acute lung injury (ALI) is a serious health-threatening syndrome of intense inflammatory response in the lungs, with progression leading to acute respiratory distress syndrome (ARDS). Dachengqi decoction dispensing granule (DDG) has a pulmonary protective role, but its potential modulatory mechanism to alleviate ALI needs further excavation.This study aims to investigate the effect and potential mechanism of DDG on lipopolysaccharide (LPS)-induced ALI models in vivo and in vitro.LPS-treated Balb/c mice and BEAS-2B cells were used to construct in vivo and in vitro ALI models, respectively. Hematoxylin-eosin (HE), Wet weight /Dry weight (W/D) calculation of lung tissue, and total protein and Lactic dehydrogenase (LDH) assays in BALF were performed to assess the extent of lung tissue injury and pulmonary edema. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in BALF, serum, and cell supernatant. The qRT-PCR was used to detect inflammatory factors, Z-DNA binding protein 1 (ZBP1), and receptor-interacting protein kinase 1 (RIPK1) expression in lung tissues and BEAS-2B cells. Double immunofluorescence staining and co-immunoprecipitation were used to detect the relative expression and co-localization of ZBP1 and RIPK1. The effects of LPS and DDG on BEAS-2B cell activity were detected by Cell Counting Kit-8 (CCK-8). Western blot (WB) was performed to analyze the expression of PANoptosis-related proteins in lung tissues and BEAS-2B cells.In vivo, DDG pretreatment could dose-dependently improve the pathological changes of lung tissue in ALI mice, and reduce the W/D ratio of lung, total protein concentration, and LDH content in BALF. In vitro, DDG reversed the inhibitory effect of LPS on BEAS-2B cell viability. Meanwhile, DDG significantly reduced the levels of inflammatory factors in vitro and in vivo. In addition, DDG could inhibit the expression levels of PANoptosis-related proteins, especially the upstream key regulatory molecules ZBP1 and RIPK1.DDG could inhibit excessive inflammation and PANoptosis to alleviate LPS-induced ALI, thus possessing good anti-inflammatory and lung-protective effects. This study establishes a theoretical basis for the further development of DDG and provides a new prospect for ALI treatment by targeting PANoptosis.Copyright © 2024. Published by Elsevier B.V.