目的 基于网络药理学和动物实验探究升降散治疗急性肺损伤（ALI）的作用机制。方法 在中药系统药理学分析平台数据库（TCMSP）和Swiss Target Prediction数据库中检索升降散的成分及靶点，在基因数据库（Gene Cards）中检索ALI的疾病靶点。将药物与疾病交集靶点上传至STRING数据平台进行蛋白质-蛋白质相互作用（PPI）分析，运用DAVID网站进行基因本体（GO）富集分析和京都基因与基因组百科全书（KEGG）通路分析。体内实验，除对照组外，升降散各给药组分别ig给药20 mL·kg^-1药液（散剂、水煎液高、低剂量分别为175、350 mg·kg^-1），每天早晚各1次，共连续给药14 d；地塞米松组第12天开始ip地塞米松（5 mg·kg^-1），连续给药3 d；除对照组外，其余各组第15天分别向气管内滴注1 mg·mL^-1脂多糖（5 mg·kg^-1）进行造模，观察肺组织病理损伤情况，ELISA法检测白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）水平，实时荧光半定量聚合酶链式反应（qRT-PCR）法检测Toll样受体4 （TLR4）、磷酸化-丝裂原活化蛋白激酶p38 （p38-MAPK）、细胞外调节蛋白激酶（ERK）、c-Jun氨基末端激酶（JNK-1） mRNA表达量，Western blotting法检测核因子κB（NF-κB）和人核因子κB抑制蛋白α（IκBα）表达量。结果 网络药理学预测出升降散活性成分32个，关键靶点292个，ALI疾病靶点有1 454个，两者交集靶点95个；升降散治疗ALI的关键靶点主要参与NF-κB、MAPK等信号通路。通过ALI小鼠模型实验结果显示，升降散能够显著减轻ALI小鼠肺部组织炎症，改善肺泡间隔及肺泡壁增厚程度；降低血清中炎症因子IL-6、IL-1β、TNF-α的水平（P＜0.05、0.01）；下调TLR4、p38-MAPK、ERK、JNK-1 mRNA的表达量（P＜0.05、0.01）；Western blotting结果表明升降散可通过抑制NF-κB蛋白磷酸化水平（P＜0.01），激活IκBα蛋白（P＜0.01），缓解ALI。结论 升降散能够基于多成分、多靶点、多通路的特点相互协同治疗ALI，其机制可能与NF-κB、MAPK等信号通路有关，且散剂治疗ALI的作用优于水煎液。

Objective To explore the mechanism of Shengjiang Powde in the treatment of acute lung injury (ALI) based on network pharmacology and animal experiments. Methods The components and targets of Shengjiang Powder were searched in Traditional Chinese Medicine Systems Pharmacology Analysis Platform Database (TCMSP) and Swiss Target Prediction Database, and the disease targets of ALI were searched in Gene Cards Database. The drug-disease intersection targets were uploaded to the STRING data platform for protein interaction analysis. Gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed using the DAVID website. In order to further explore the effect of Shengjiang Powder on ALI, a mouse ALI model was established to observe the pathological damage of lung tissue. In addition to the control group, each administration group of Shengjiang Powder was ig administered with 20 mL·kg^?1 drug solution (the doses of powder, water decoction and its high and low dose groups were 175 and 350 mg·kg^?1, respectively, once a day in the morning and evening, for a total of 14 days). On the 12 th day, dexamethasone (5 mg·kg^?1) was injected intraperitoneally for three days. On the 15th day, 1 mg·mL^?1 lipopolysaccharide (5 mg·kg^?1) was instilled into the trachea for modeling. The levels of interleukin 6 (IL-6),interleukin 1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected by ELISA. The mRNA expressions of Toll-like receptor 4 (TLR4), phosphorylated-mitogen-activated protein kinase p38 (p38-MAPK), extracellular regulated protein kinases (ERK), c-Jun Nterminal kinase (JNK-1) were detected by RT-PCR. Protein expressions of nuclear factor kappa B (NF-κB) and human nuclear factor κB inhibitory protein α (IκBα) were detected by Western blotting. Results It was predicted that there were 32 active components, 292 key targets, 1 454 ALI disease targets and 95 intersection targets of Shengjiang Powder and ALI. The key targets of Shengjiang Powder in the treatment of ALI were mainly involved in NF-κB, MAPK and other signaling pathways. The results of ALI mouse model showed that Shengjiang Powder could significantly reduce the inflammation of lung tissue in ALI mice and improve the thickening of alveolar septum and alveolar wall. Shengjiang Powder could reduce the content of inflammatory factors IL-6, IL-1β and TNF-α in serum. The expression of TLR4, p38-MAPK, ERK and JNK-1 mRNA was down-regulated. Western blotting results showed that Shengjiang Powder could activate IκBα protein and alleviate ALI by inhibiting the phosphorylation level of NF- κB protein. Conclusion Shengjiang Powder can synergistically treat ALI based on the characteristics of multi-component, multi-target and multi-pathway. The mechanism may be related to NF-κB, MAPK and other signaling pathways, and the effect of Shengjiang Powder on ALI is better than that of water extract.

R285.5

中医药事业传承发展资金支持项目（吉中医药发［2021］11号）