基于网络药理学和实验验证探讨麦冬皂苷D治疗肺纤维化的作用机制  

Mechanism of ophiopogonin D in treatment of pulmonary fibrosis based on network pharmacology and experimental verification

作　　者：彭文潘 徐泳 周运海[1] 吴娟娟[1] 彭贵清 顾燕兰 余松 浦明之[1] PENG Wen-pan;XU Yong;ZHOU Yun-hai;WU Juan-juan;PENG Gui-qing;GU Yan-lan;YU Song;PU Ming-zhi(Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine,Suzhou,Jiangsu 215009,China;Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China)

机构地区：[1]南京中医药大学附属苏州市中医医院,江苏苏州215009 [2]南京中医药大学中医学院·中西医结合学院,江苏南京210029

出　　处：《中国药理学通报》2023年第8期1557-1565,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82074358);苏州市医学重点学科建设(No SZXK202112);苏州市科技发展计划项目(No SKJYD2021124);苏州市姑苏卫生人才计划(No GSWS2022080)。

摘　　要：目的运用网络药理学预测麦冬皂苷D(Ophiopogonin D,OPD)抗肺纤维化潜在作用机制,进一步通过小鼠体内实验进行验证。方法本研究通过数据挖掘发现麦冬为治疗气阴两虚型肺纤维化使用频率最高的中药,为探究其物质基础,对其进行网络药理学分析。通过博来霉素构建肺纤维化小鼠模型,并给予不同浓度的OPD干预治疗,验证网络药理学结果。结果首先通过网络药理学分析发现,线粒体自噬可能是麦冬发挥抗肺纤维化作用的潜在靶点,同时对网络图拓扑学分析发现,活性成分麦冬皂苷D与线粒体自噬关系最大。动物实验发现,OPD能缓解小鼠肺纤维化,减少胶原沉积;同时对线粒体自噬相关蛋白检测发现,该化合物能够增加肺组织中PINK1、Parkin蛋白的表达,减少p62蛋白含量,降低细胞内ROS水平。结论OPD通过促进肺组织中PINK1/Parkin依赖的线粒体自噬,改善线粒体功能发挥抗肺纤维化作用。Aim To predict the potential mechanism of ophiopogonin D(OPD)against pulmonary fibrosis by network pharmacology,and further verify it by experiment in vivo.Methods This study found that ophiopogon was the most frequently used drug in the treatment of pulmonary fibrosis with deficiency of Qi and Yin through data mining.In order to explore its material basis,network pharmacology analysis was carried out.A model of pulmonary fibrosis was established by bleomycin,and different concentrations of ophiopogonin D were administered to verify the results of the pharmacological network.Results Firstly,through network pharmacology analysis,it was found that mitophagy might be the potential target for ophiopogon to exert anti-pulmonary fibrosis effect.Meanwhile,network topology analysis showed that OPD had the greatest relationship with mitophagy.Animal experiments showed that OPD could relieve pulmonary fibrosis and reduce collagen deposition in mice.At the same time,the detection of mitophagy related proteins showed that the compound could increase the expression of PINK1 and Parkin proteins,reduce the content of P62 protein in lung tissue,and reduce the intracellular ROS level.Conclusions OPD can improve mitochondrial function and play an anti-pulmonary fibrosis role by promoting PINK1/Parkin dependent mitophagy in lung tissue.

关 键 词：肺纤维化 麦冬皂苷D 网络药理学 博来霉素 线粒体自噬 PINK1/Parkin 

分 类 号：R-332[医药卫生] R284.1R319R329.24R563.13