目的 探讨白花蛇舌草水提物（HDAE）对脂多糖（LPS）诱导急性肺损伤（ALI）大鼠的改善作用及分子机制。方法 通过高通量基因表达数据库（GEO）筛选ALI差异基因，受试者工作特征曲线（ROC）来验证差异基因。SD大鼠随机分为对照组、模型（LPS，5 mg·kg^-1）组、地塞米松（阳性药，2.5 mg·kg^-1）组和HDAE高、中、低剂量（300、200、100 mg·kg^-1）组，除对照组外，采用LPS（5 mg·kg^-1）诱导ALI大鼠模型，苏木精-伊红（HE）染色观察肺组织病理变化；酶联免疫吸附测定法（ELISA）检测大鼠血清中白细胞介素（IL）-10、IL-1β变化；免疫组化检测肺组织IL-6、肿瘤坏死因子（TNF）-α水平；免疫荧光检测IL^-17、核因子（NF）-κB p65蛋白水平。结果 通过相互作用及通路分析发现NF-κB、TNF、IL6等为ALI差异基因枢纽，促炎因子（IL1β、TNF-α）通过激活NF-κB通路发挥作用；另一方面上调IL^-17通路关键分子，形成NF-κB与IL^-17通路的正反馈放大回路，其中关键特征基因为TNF、IL-6。与模型组比较，HE染色结果显示，HDAE可减轻LPS诱导的肺部损伤； HDAE组大鼠IL-1β水平显著下降（P＜0.05），IL^-10水平显著提高（P＜0.05），肺组织内IL-6、TNF-α、IL^-17、NF-κB p65蛋白的表达明显下调（P＜0.01）。结论 HDAE靶向调控IL^-17、NF-κBp65信号通路，进而干预IL-6、TNF-α的表达，对LPS诱导的ALI大鼠发挥保护作用。

Objective To explore the ameliorative effect and molecular mechanism of Hedyotis diffusa water extract (HDAE) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. Methods ALI-related differentially expressed genes were screened through the high-throughput gene expression database (GEO), and the differentially expressed genes were verified by receiver operating characteristic curve (ROC). SD rats were randomly divided into the control group, the model (LPS, 5 mg·kg^-1) group, the dexamethasone (positive drug, 2.5 mg·kg^-1) group, and the HDAE high-, medium-, and low-dose (300, 200, 100 mg·kg^-1) groups. Except for the control group, ALI rat models were induced by LPS (5 mg·kg^-1). Hematoxylin-eosin (HE) staining was used to observe the pathological changes in lung tissue; enzyme-linked immunosorbent assay (ELISA) was used to detect the changes in interleukin (IL)-10 and IL^-1β in rat serum; immunohistochemistry was used to detect the levels of IL-6 and TNF-α in lung tissue; and immunofluorescence was used to detect the protein levels of IL^-17 and NF-κB p65. Results Through interaction and pathway analysis, it was found that NF-κB, TNF, IL6, etc. were the hub genes of ALI differentially expressed genes. Pro-inflammatory factors (IL1β, TNF-α) exerted their effects by activating the NF-κB pathway. On the other hand, they upregulated the key molecules of the IL- 17 pathway, forming a positive feedback amplification loop between the NF-κB and IL^-17 pathways, with TNF and IL-6 as the key characteristic genes. Compared with the model group, HE staining results showed that HDAE could alleviate LPS-induced lung injury; the IL^-1β level in the HDAE group was significantly decreased (P<0.05), and the IL^-10 level was significantly increased (P<0.05). The expression of IL-6, TNF-α, IL^-17, and NF-κB p65 proteins in lung tissue was significantly downregulated (P<0.01). Conclusion HDAE targets the regulation of the IL^-17 and NF-κB p65 signaling pathways, thereby interfering with the expression of IL-6 and TNF- α, and exerts a protective effect on LPS-induced ALI in rats.

R285.5

贵州省基础研究计划面上项目（黔科合基础MS〔2026〕 656）；贵州中医药大学国家与省级科技创新人才团队培育项目（贵中医TD合字[2022]004号）