整合动物实验和网络药理学探讨蛹虫草改善慢性阻塞性肺疾病的药效机制

Pharmacological Mechanism of Cordyceps militaris in Improving Chronic Obstructive Pulmonary Disease Based on Animal Experiment and Network Pharmacology

  • 摘要:
    目的 探究蛹虫草改善慢性阻塞性肺疾病(COPD)的药效作用及其相关机制。
    方法 采用香烟烟熏联合脂多糖(LPS)鼻滴方法将C57小鼠建立成为COPD模型,以肺功能数据作为药效学考察指标,使用网络药理学技术预测蛹虫草改善COPD机制,并通过qPCR和Western blot进行相关机制验证。
    结果 蛹虫草能够显著改善吸气峰值流速(PIF)、呼气峰值流速(PEF)、呼吸中期流速(EF50)、小鼠潮气量(TV)、深吸气量(IC)、呼吸系统顺应性(Crs)等多项肺功能指标(P<0.05)。网络药理学研究表明蛹虫草改善COPD可能与基质金属蛋白酶(MMPs)有关。qPCR和Western blot结果表明蛹虫草能显著降低小鼠肺组织MMP-2、MMP-9和MMP-12的mRNA和蛋白表达(P<0.05)。
    结论 蛹虫草能够通过降低MMP-2、MMP-9与MMP-12的水平,改善COPD模型小鼠PIF、PEF、EF50、TV、IC和Crs六项肺功能指标,达到治疗COPD的作用。

     

    Abstract:
    OBJECTIVE To investigate the effects and mechanism of Cordyceps militaris in the treatment of chronic obstructive pulmonary disease (COPD).
    METHODS The COPD model was established using C57 mice by combining cigarette smoke exposure and intranasal lipopolysaccharides (LPS). Lung-function indexes were used as the pharmacological indicators. Network pharmacology was employed to predict the mechanism of Cordyceps militaris in improving COPD. Real-time fluorescence quantitative PCR and Western blot were used to verify the related mechanism in lung tissues.
    RESULTS Cordyceps militaris significantly improved several lung function data such as peak inspiratory flow rate (PIF), peak expiratory flow rate (PEF), tidal volume (TV), mid-respiratory flow rate (EF50), inspiratory capacity (IC), and respiratory system compliance (Crs) of COPD mice (P<0.05). Network pharmacology studies suggested that the improvement of COPD by Cordyceps militaris might be related to matrix metalloproteinases (MMPs). The results of PCR and Western blot showed that Cordyceps militaris significantly reduced the expression of MMP-2, MMP-9 and MMP-12 mRNA and protein in lung tissue (P<0.05).
    CONCLUSION Cordyceps militaris could improve six lung functions of mice, including PIF, PEF, EF50, TV, IC, and Crs, by reducing the levels of MMP-2, MMP-9, and MMP-12, thus achieving the therapeutic effect on COPD.

     

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