基于生物网络和代谢组学研究蒲地蓝消炎口服液抗LPS诱导小鼠急性呼吸道感染的作用机制  

The mechanism of action of Pudilan Xiaoyan oral liquid against LPS-induced acute respiratory infection in mice based on biological network analysis and metabolomics

作　　者：田刚 胡远卓 李超 翟园园 包贝华[2] 姚卫峰[2] 张丽[2] 丁安伟[2] TIAN Gang;HU Yuan-zhuo;LI Chao;ZHAI Yuan-yuan;BAO Bei-hua;YAO Wei-feng;ZHANG Li;DING An-wei(Jumpcan Pharmaceutical Co.,Ltd.,Taizhou 225411,China;School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China)

机构地区：[1]济川药业集团有限公司药物研究院,江苏泰州225411 [2]南京中医药大学药学院,江苏南京210023

出　　处：《药学学报》2021年第3期816-822,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81973445)。

摘　　要：本研究整合代谢组学和网络药理学技术手段从生物网络角度系统分析蒲地蓝消炎口服液治疗急性呼吸道感染可能作用机制。GC-MS代谢组学分析从LPS诱导急性呼吸道感染小鼠血清中发现3-磷酸甘油酸、α-氨基己二酸、D-核酮糖-5-磷酸、β-甘露糖基甘油酸、D-果糖、尿素、D-麦芽糖和鸟氨酸等8个内源性代谢物可作为蒲地蓝消炎口服液治疗急性呼吸道感染的显著性生物标记物,进一步生物网络研究表明主要属于糖酵解和磷酸戊糖途径的GPI、G6PD、H6PD、PFKM、TALDO1、TKT、GAPDH、HK1、PKLR和TPI1等10个蛋白为蒲地蓝消炎口服液干预急性呼吸道感染的潜在靶点。动物实验操作均遵循南京中医药大学动物伦理委员会的规定。研究发现,代谢组学和网络分析相结合的策略有助于解释蒲地蓝消炎口服液治疗急性呼吸道感染可能作用机制,并揭示蒲地蓝消炎口服液可能通过调节紊乱的代谢途径来治疗急性呼吸道感染的病理过程。This study integrates metabolomics and network pharmacology techniques to systematically analyze the possible mechanism of Pudilan Xiaoyan oral liquid(PDL)in the treatment of acute respiratory infections.GCMS metabolomics analysis found 8 endogenous metabolites,3-phosphoglycerate,α-aminoadipate,D-ribulose-5-phosphate,β-mannosylglyceric acid,D-fructose,urea,D-maltose and ornithine in the serum of mice with acute respiratory infection induced by LPS;these substances can be used as biomarkers for PDL use in the treatment of acute respiratory infections.Biological network studies revealed 10 potential targets for intervention by PDL in the glycolysis and pentose phosphate pathways,including GPI,G6 PD,H6 PD,PFKM,TALDO1,TKT,GAPDH,HK1,PKLR and TPI1.All animal experiments were carried out with approval of the Animal Ethics Committee of Nanjing University of Chinese Medicine.Our findings indicate that the strategy of combining metabolomics and network analysis can provide information on the possible mechanism of PDL in acute respiratory infections,and reveal that PDL may ameliorate the pathological process of acute respiratory infections by regulating disordered metabolic pathways.

关 键 词：蒲地蓝消炎口服液 网络药理学 代谢组学 LPS 急性呼吸道感染 

分 类 号：R917[医药卫生—药物分析学]