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目的 探讨小儿清热宣肺贴膏对支原体肺炎(MPP)小鼠肺损伤的影响、相关机制及体外透皮研究。方法 应用网络药理学预测小儿清热宣肺贴膏的核心成分、靶点基因及主要通路，通过分子对接，结合肺炎支原体感染Balb/c小鼠模型对上述预测靶点与通路进行验证。采用SD大鼠进行体外透皮实验验证。使用改良Franz扩散池法，以离体SD大鼠皮作为体外透皮模型，生理盐水为接收液，利用HPLC法研究小儿清热宣肺贴膏中栀子苷与羟基红花黄色素A的透皮行为。结果 网络药理学结果显示小儿清热宣肺贴膏作用于768个靶点，MPP有2136个相关靶点，得到“药物-疾病”交集靶点299个，KEGG富集分析发现核心靶点主要作用于磷脂酰肌醇3激酶(PI3K)-蛋白激酶 B(Akt)、肿瘤坏死因子(TNF)、HIF-1等信号通路，分子对接结果表明药物成分与靶点结合良好。实验结果进一步表明，小儿清热宣肺贴膏可通过调控MPP引起的PI3K-Akt等信号通路失调，下调肿瘤坏死因子α(TNF-α)等炎性因子表达。体外透皮实验表明，栀子苷与羟基红花黄色素A 12 h平均累积透过量分别为260.45 μg/cm2与804.28 μg/cm2，12 h稳态透皮速率分别为22.157 μg/(cm2·h)与43.860 μg/(cm2·h)，指标成分的体外透皮过程符合零级动力学方程。结论 小儿清热宣肺贴膏可能通过多成分、多靶点和多通路干预MPP，其机制可能与调节PI3K-Akt等信号通路及TNF-α等炎性因子有关；建立的HPLC含量测定方法稳定、可靠，贴膏可能通过缓慢释放栀子苷与羟基红花黄色素A起到干预MPP的作用。
Abstract：Objective To determine the effect of Xiaoer Qingre Xuanfei plaster on mycoplasma pneumoniae pneumonia (MPP)-induced lung injury in mice,its in vitro transdermal permeation,and underlying mechanism.Methods Network pharmacology was used to predict the core components,target genes,and key pathways of the plaster.Molecular docking and an MPP-infected Balb/c mouse model were used to validate these predictions.An?in vitro?transdermal permeation study was conducted with a modified Franz diffusion cell with excised SD rat skin and saline as the receptor medium.HPLC was utilized to evaluate the transdermal behavior of geniposide and hydroxysafflor yellow A.Results Totally 768 drug targets and 2136 disease-related targets were identified,including 299 overlapping targets.KEGG enrichment analysis indicated that the core targets were associated with PI3K-Akt,TNF,and HIF-1 signaling pathways.Molecular docking confirmed strong binding between drug components and targets.Experimental results demonstrated that the plaster alleviated MPP-induced lung injury by regulating PI3K-Akt pathway dysregulation and reducing TNF-α expression.In vitro?transdermal studies showed that the 12-hour cumulative permeation amounts of geniposide and hydroxysafflor yellow A were 260.45 μg/cm2 and 804.28 μg/cm2,respectively,with steady-state transdermal rates at 22.157 μg/(cm2·h) and 43.860 μg/ (cm2·h).The permeation kinetics followed a zero-order model.Conclusion Xiaoer Qingre Xuanfei plaster exerts therapeutic effect against MPP through multi-component,multi-target,and multi-pathway mechanisms,potentially involving modulation of the PI3K-Akt pathway and inflammatory cytokines such as TNF-α.A stable and reliable HPLC method is successfully developed and validated,suggesting that the therapeutic effect of the plaster against MPP may be mediated by the sustained release of geniposide and hydroxysafflor yellow A.
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基本信息:
中图分类号:R285.5
引用信息:
[1]凌京平,王雪峰,史俊祖,等.基于网络药理学及实验验证的小儿清热宣肺贴膏干预支原体肺炎机制研究[J].中南药学,2026,24(01):32-40.
基金信息:
国家传承创新中心重点病种项目(No.2023-247)
2026-01-20
2026-01-20