Dachengqi汤剂分配颗粒可通过抑制体内和体外延伸来缓解LPS诱导的急性肺损伤

急性肺损伤（ALI）是一种严重的威胁健康综合征，对肺部强烈炎症反应，进展导致急性呼吸遇险综合征（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和体外ALI模型。在BALF中进行了肺蛋白 - 烯烃（HE），肺组织的湿重/干重（W/D）计算，总蛋白质和乳酸脱氢酶（LDH）测定法，以评估肺组织损伤和肺水肿的程度。酶联免疫吸附测定（ELISA）用于检测肿瘤坏死因子 - α（TNF-α），白介素-1β（IL-1β）和白介素-18（IL-18）（IL-18）在BAL，血清和细胞和细胞超级NEC8（IL-18）。 QRT-PCR用于检测肺组织和BEAS-2B细胞中的受体相互作用蛋白激酶1（RIPK1）表达的炎症因子Z-DNA结合蛋白1（ZBP1）和受体相互作用的蛋白激酶。双重免疫荧光染色和共免疫沉淀用于检测ZBP1和RIPK1的相对表达和共定位。通过细胞计数KIT-8（CCK-8）检测到LPS和DDG对BEAS-2B细胞活性的影响。进行了蛋白质印迹（WB）以分析肺组织和BEAS-2B细胞中全全变相关蛋白的表达。在体内，DDG预处理可以依赖性地依赖性地改善ALI小鼠中肺组织的病理变化，并降低肺，蛋白质浓度和LDH含量的肺部W/D比。在体外，DDG逆转了LPS对BEAS-2B细胞活力的抑制作用。同时，DDG显着降低了体外和体内炎症因子的水平。此外，DDG可以抑制与全全变相关蛋白的表达水平，尤其是上游关键的调节分子ZBP1和RIPK1.DDG可以抑制过度的炎症和全全变，从而减轻LPS诱导的ALI，从而具有良好的抗炎性和肺部抗炎和肺部效果。这项研究为DDG的进一步发展建立了理论基础，并通过靶向全全变为ALI治疗提供了新的前景。

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.