| 吴鉴超；赵源；陈久林；刘特；郁志华.贝母瓜蒌散抑制炎症反应改善脂多糖诱导小鼠急性肺损伤的机制研究[J].中医药信息,2023,40(11):13-22 |
| 贝母瓜蒌散抑制炎症反应改善脂多糖诱导小鼠急性肺损伤的机制研究 |
| Study on Mechanism of Inhibiting Inflammatory Response and Improving Lipopolysaccharide Induced Acute Lung Injury in Mice with Beimu Gualou Powder |
| 投稿时间：2023-04-07 录用日期：2023-06-12 |
| DOI：10.19656/j.cnki.1002-2406.20231103 |
| 中文关键词: 贝母瓜蒌散 急性肺损伤 网络药理学 炎症因子 脂多糖 |
| 英文关键词: Beimu Gualou Powder Acute lung injury Internet pharmacology Inflammatory factors Lipopolysaccharide |
| 基金项目:上海市高校高峰学科建设项目 |
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| 中文摘要: |
| 目的：基于网络药理学和脂多糖诱导的小鼠急性肺损伤模型探究贝母瓜蒌散干预急性肺损伤（acute lung injury,ALI）的抗炎作用。方法：通过中医药系统药理学数据库和分析平台，以生物利用度和药物相似性为条件筛选贝母瓜蒌散活性成分和作用靶点；在GeneCards数据库获取ALI相关靶基因。通过STRING平台构建化合物靶点-ALI靶基因相互作用（protein-protein interaction,PPI）网络，运用Cytoscape 3.8. 0软件构建药材-成分-靶点-通路网络，利用Metascape平台进行基因本体（gene ontology,GO）分析，应用通路数据库Reactome进行信号通路富集分析，预测其分子机制。通过贝母瓜蒌散对脂多糖诱导的急性肺损伤小鼠的干预实验，对潜在靶点和通路进行验证。结果：获得贝母瓜蒌散活性成分44个、靶点606个，与ALI有关共同靶点258个。GO功能富集分析发现，贝母瓜蒌散对ALI的作用主要涉及激酶活性的正调控、受体复合物、蛋白激酶活性等过程；通路富集分析指出，贝母瓜蒌散可能从调控白细胞介素信号、白介素-4和白介素-13的信号、免疫系统中的细胞因子信号传递等信号通路发挥治疗作用。HE染色及胶原纤维阳性染色结果显示，贝母瓜蒌散能改善肺损伤；qPCR结果显示，贝母瓜蒌散能下调小鼠肺组织IL-1α、IL-2、IL6、IL-10、TNF-α mRNA表达。结论：贝母瓜蒌散可能通过抑制促炎细胞因子表达发挥治疗ALI的作用。 |
| 英文摘要: |
| Objective: To explore the anti-inflammatory effect of Beimu Gualou Powder(BGP) in acute lung injury(ALI)based on network pharmacology and lipopolysaccharide-induced acute lung injury in mice.Methods: The active ingredients and targets of BGP were screened based on the conditions of bioavailability and drug similarity through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and ALI related target genes were obtained from GeneCards database. A compound target-ALI target gene interaction(protein-protein interaction, PPI) network was constructed through STRING platform; a medicinal material-component-target-pathway network was created using Cytoscape 3. 8. 0 software; gene ontology(GO) analysis was performed through Metascape platform; enrichment analysis of Signaling pathway was conducted using pathway database Reactome to predict its molecular mechanism.The intervention experiment of BGS on lipopolysaccharids-induced acute lung injury in mice was carried out to verify the potential targets and pathways. Results: We obtained 44 active components and 606 targets of BGS, and 258 of the targets have common targets with ALI. We found through Go functional enrichment analysis that the effects of BGS on ALI mainly involve processes such as positive regulation of kinase activity, receptor complex, and protein kinase activity. Pathway enrichment analysis indicated that BGS may exert therapeutic effects by the regulation of signaling pathways such as interleukin signaling, interleukin-4, interleukin-13 signaling, and cytokine signaling in the immune system. The results of HE staining and positive staining of collagen fibers showed that BGS could improve lung injury; and the results of qPCR showed that BGS could downregulate mRNA expressions of IL-1α, IL-2, IL6, IL-10, and TNF-α in of mouse lung tissues. Conclusion: Beimu Gualou Powder may exert therapeutic effects against ALI by inhibiting proinflammatory cytokine expression. |
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