目的 探讨藤黄酸（gambogic acid, GA）对脂多糖（lipopolysaccharide, LPS）诱导急性肺损伤（acute lung injury, ALI）的保护作用及机制。 方法 建立LPS诱导的ICR小鼠ALI模型及人支气管上皮细胞系BEAS‑2B细胞模型，分为对照组、LPS组、GA（低、中、高）剂量组及地塞米松组。采用苏木精-伊红染色评估小鼠肺组织的病理损伤程度并进行评分，检测肺指数。采用MTS法检测GA与地塞米松对细胞活力的影响，苏木精-伊红染色观察BEAS‑2B细胞的形态变化。采用联合转录组测序与分子对接技术预测GA的潜在作用靶点与通路。采用蛋白质印迹法检测细胞模型和动物模型中的肿瘤坏死因子‑α、白细胞介素（interleukin, IL）‑6、IL‑1β、凋亡调节蛋白Bcl‑2相关X蛋白、B细胞淋巴瘤‑2的表达水平，以及MAPK途径关键蛋白p38、胞外信号调节激酶（extracellular signal‑regulated kinase, ERK）、c‑Jun氨基端激酶（c‑Jun N‑terminal kinase, JNK）的磷酸化程度。 结果 与LPS组相比，GA中剂量组、GA高剂量组、地塞米松组小鼠肺损伤评分、肺指数降低（P<0.05），BEAS‑2B细胞结构损伤减轻。在细胞模型和小鼠模型中，与LPS组相比，GA中剂量组、GA高剂量组、地塞米松组肿瘤坏死因子‑α、IL‑6、IL‑1β等促炎因子表达降低（P<0.05）。各组BEAS‑2B细胞活力比较，差异无统计学意义（P>0.05）。转录组学结果提示，GA可能通过调节MAPK途径干预ALI。分子对接结果显示，GA可与p38、JNK及ERK蛋白稳定结合。细胞模型和小鼠模型实验均表明，GA中剂量组和GA高剂量组可抑制LPS诱导的p38、ERK及JNK磷酸化激活（P<0.05），并抑制LPS诱导的Bcl‑2相关X蛋白/B细胞淋巴瘤‑2比值增加（P<0.05）。 结论 GA可减轻LPS诱导的ALI，其机制可能与抑制MAPK途径，发挥抗炎及抗凋亡效应有关。

Objective To investigate the protective effects and mechanisms of gambogic acid (GA) against lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods An in vivo ALI model was established in ICR mice by LPS administration, and an in vitro model was established in LPS-stimulated BEAS-2B human bronchial epithelial cells. Mice were divided into control, LPS, GA (low, medium, and high doses), and dexamethasone groups. BEAS-2B cells were stimulated with LPS alone or co-treated with GA (low, medium, or high dose) or dexamethasone. Lung histopathology was evaluated by hematoxylin-eosin staining and scored, and the lung index was measured. In vitro, cell viability was assessed by MTS assay, and morphological changes were observed by hematoxylin-eosin staining. Transcriptome sequencing combined with molecular docking was used to predict potential targets and pathways of GA. In cells and mice, Western blotting was used to detect tumor necrosis factor-α, interleukin (IL)-6, IL-1β, the expression of B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax), and the phosphorylation of mitogen-activated protein kinase (MAPK) pathway proteins [p38, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK)]. Results Compared with the LPS group, the GA medium- and high-dose groups and the dexamethasone group showed reduced lung injury scores and lung index (P<0.05), and alleviated structural damage in BEAS-2B cells. In both models, these groups exhibited decreased expression of TNF-α, IL-6, and IL-1β relative to the LPS group (P<0.05). There was no significant difference in BEAS-2B cell viability among groups (P>0.05). Transcriptomic analysis suggested that GA may attenuate ALI by modulating the MAPK pathway. Molecular docking analysis indicated stable binding of GA to p38, JNK, and ERK. In both models, medium- and high-dose GA inhibited LPS-induced phosphorylation of p38, ERK, and JNK (P<0.05) and suppressed the LPS-induced increase in the Bax/Bcl-2 ratio (P<0.05). Conclusions GA attenuates LPS-induced ALI, possibly by inhibiting the MAPK pathway and exerting anti-inflammatory and anti-apoptotic effects.