中药川芎治疗脊髓损伤的网络药理学研究

Network Pharmacology on Treatment of Spinal Cord Injury with Chuanxiong (Ligusticum Chuanxiong)

目的基于网络药理学研究探讨川芎在脊髓损伤(SCI)治疗中的潜在作用机制。方法基于所得化合物的口服药物生物利用度(OB)和类药性(DL),在中药系统药理学技术平台(TCMSP)等数据库预测并筛选川芎的化合物及治疗脊髓损伤的作用靶点。在Cytoscape 3.5.1软件上构建川芎化合物-靶点网络,使用STRING构建靶点蛋白相互作用网络,生物学信息注释数据库(DAVID)用于对靶点基因本体(GO)生物过程及京都基因与基因组百科全书(KEGG)代谢通路富集分析。结果从川芎中筛选出7个化合物,作用于43个SCI靶点,关键的靶点有超/过氧化物歧化酶1(SOD1)、一氧化氮合酶2(NOS2)、表皮生长因子(EGF)、钙结合蛋白S100B、基质金属蛋白酶9(MMP9)、烯醇化酶2(ENO2)等,参与缺氧应答、氧化还原过程、对活性氧类的反应、一氧化氮生物合成过程的正向调节、谷胱甘肽代谢过程、神经递质生物合成过程、血压的调节、超氧化物代谢过程等生物过程,富集于细胞外基质/区、髓鞘、线粒体、过氧化物酶体等,调节缺氧诱导因子-1信号通路、过氧化物酶体、能量代谢等通路。结论川芎可能主要通过调节氧化应激反应及随之而来的线粒体功能障碍以及低氧适应性的血管微环境重建、能量代谢,神经递质合成、再髓鞘,调节炎症反应等方面来治疗脊髓损伤。

Objective To study the potential mechanism of Chuanxiong(Ligusticum Chuanxiong) in the treatment of spinal cord injury(SCI) by using network pharmacology.Methods Based on the oral bioavailability(OB) and drug like(DL) of compounds,the compounds of Chuanxiong and the target of SCItherapy were predicted and screened according to databases as Traditional Chinese Medicine System Pharmacology(TCMSP) Technology Platform.Target protein interaction network was established by using STRING platform,and compound-target network of Chuanxiong was constructed by using Cytoscape 3.5.1 software.Biological processes of target gene ontology(GO) and metabolic pathways in Kyoto Encyclopedia of Genes and Genomes(KEGG)were analyzed by DAVID,a database of biological information.Results Seven compounds were screened from Chuanxiong(Ligusticum Chuanxiong),which mainly acted on 43 targets of SCI.The key targets included SOD1,NOS2,EGF,S100 B,MMP9 and ENO2,participating in many biological processes such as oxidation-reduction process,oxidation-reduction process,response to reactive oxygen species,positive regulation of nitric oxide biosynthetic process,glutathione metabolic proces,neurotransmitter biosynthetic process,regulation of blood pressure and superoxide metabolic process,enriched in extracellular matrix/region,myelin sheath,mitochondria,peroxisome and so on,regulating KEGG signal pathways such as HIF-1 signaling pathway,Peroxisome and Metabolic pathways.Conclusion Chuanxiong(Ligusticum Chuanxiong) may treat spinal cord injury mainly through regulating oxidative stress response,mitochondrial dysfunction and hypoxic adaptation to vascular microenvironment reconstruction,energy metabolism,neurotransmitter synthesis,re-myelination and inflammatory response.