【摘要】 目的 通过生物信息学分析以及动物实验验证相结合的方法，探讨五苓益肺汤治疗哮喘的潜在关键靶点和相关的信号通路，为该方的开发提供实验依据。方法 采用网络药理学方法筛选五苓益肺汤治疗哮喘的核心靶点和通路。雄性SD大鼠于第1、8、15日腹腔注射1 mL卵清蛋白致敏液，第22～28日给予10μL/鼻孔卵清蛋白激发液滴鼻。首次致敏后2 h给予相应药物灌胃治疗。最后一次滴鼻激发24 h内取血、取肺组织、取肺泡灌洗液，检测免疫和炎症指标，并观察肺组织TLR4、NF-κB表达情况。结果 网络药理学筛选出五苓益肺汤治疗哮喘的核心靶点AKT1、IL6、JUN、IL1B、IKBKB、MAPK8等51个，KEGG富集分析获得TLR4/NF-κB等通路146条。动物实验结果显示，与模型组相比，五苓益肺汤能升高胸腺指数，CD8~+；降低脾指数，血清IgE,CD4~+、CD4~+/CD8~+和肺泡灌洗液中及肺组织匀浆中SOD、白细胞、淋巴细胞数量和TNF-α、TGF-β、IL-1β、IL-6水平及MDA表达；减少肺组织炎性细胞浸润，改善肺泡间隔增厚、结构不清晰情况；减少肺组织中TLR4和NF-κB p65的表达。结论五苓益肺汤能有效减轻大鼠的哮喘，其机制可能与调节TLR4/NF-κB通路有关。更多还原

【Abstract】 Objective To determine the potential key targets and related signaling pathways of Wuling Yifei decoction(WLYFT) for asthma and to provide an experimental basis for the development of this formula, through mutually integrated approach of bioinformatics analysis and animal experimental validation. Methods A network pharmacology approach was used to screen the core targets and pathways of WLYFT for asthma. Male SD rats were intraperitoneally injected 1 mL OVA sensitizing solution on day 1, 8 and 15, and nasal drops(10 μL/nostril) OVA stimulating solution on day 22 ～ 28.Drugs were given orally 2 h after the first sensitization. Blood, lung tissue and alveolar lavage were collected within 24 hours after the last nasal drip to test the immune and inflammatory indexes and the expression of TLR4 and NF-κB in the lung tissue were observed. Results Totally 51 core targets of WLYFT for asthma were screened by network pharmacology, including AKT1, IL6, JUN, IL1B,IKBKB, MAPK8, etc, and 146 pathways such as TLR4/NF-κ B were obtained by KEGG analysis.Compared with the model group, WLYFT increased thymic index, CD8~+, SOD; decreased spleen index, serum IgE, CD4~+, CD4~+/CD8~+, IL-6, IL-1β, TNF-α and TGF-β contents in alveolar lavage fluid, and MDA in the lung tissue homogenate; improved unclear lung tissue structure, bronchial wall smooth muscle thickening, alveolar lumen enlargement, alveolar wall thickening; and reduced the inflammatory cell infiltration, the expression of TLR4 and NF-κB p65 in the lung tissues. Conclusion WLYFT can effectively alleviate asthma in rats, and the mechanism may be related to the regulation of TLR4/NF-κB pathway.更多还原