基于网络药理学探讨丹参酮ⅡA治疗脊髓损伤的可能机制及相关通路

Exploring the Possible Mechanism and Related Pathways of Tanshinone ⅡA in the Treatment of Spinal Cord Injury Based on Network Pharmacology

目的:基于网络药理学分析丹参酮ⅡA治疗脊髓损伤的分子生物学机制及相关通路。方法:利用TCMSP、BATMAN-TCM、DTPS、STITCHI、Swiss Target Prediction 5个数据库筛选出丹参酮ⅡA的作用靶点,利用OMIM、GeneCards、CTD数据库检索脊髓损伤相关基因,利用韦恩图筛选丹参酮ⅡA治疗脊髓损伤的作用靶点。利用STRING数据库进行蛋白互作网络分析,利用Cytoscape软件构建蛋白相互作用网络,利用Metascape数据库进行GO分析和KEGG信号通路富集分析。结果:丹参酮ⅡA共有潜在靶点182个,与脊髓损伤相关的靶点157个,其中肿瘤蛋白p53(TP53)、Myc原癌基因蛋白(MYC)、G1/S-特异性周期蛋白-D1(CCND1)、半胱氨酸天冬氨酸蛋白酶3(CASP3)、JUN原癌基因蛋白(JUN)5个靶点在蛋白互作网络中具有较为重要的作用。丹参酮ⅡA治疗脊髓损伤涉及的生物学过程主要包括药物反应、脂多糖反应、细胞对DNA损伤刺激的反应等;涉及的分子功能主要包括酶结合、转录因子结合、蛋白结合等。其作用机制可能与cAMP signaling pathway、MAPK signaling pathway、PI3K-Akt signaling pathway、HIF-1 signaling pathway、TNF signaling pathway、Apoptosis等通路有关。结论:丹参酮ⅡA治疗脊髓损伤具有多靶点、多通路作用的特点,其可能通过促进神经元存活、促进轴突再生、抑制神经细胞凋亡、抗炎等过程对脊髓损伤过程进行干预。

Objective:To analyze the molecular biological mechanism and related pathways of spinal cord injury by tanshinoneⅡA based on network pharmacology.Methods:The target sites of tanshinoneⅡA were screened by TCMSP,BATMAN-TCM,DTPS,STITCHI and Swiss Target Prediction.The genes related to spinal cord injury were searched by OMIM,GeneCards and CTD databases,and the target of the spinal cord injury was screened by Wayne map.The STRING database was used for protein interaction network analysis.The protein interaction network was constructed by Cytoscape software,and the Metascape database was used for GO analysis and KEGG signal pathway enrichment analysis.Results:TanshinoneⅡA had a total of 182 potential targets and 157 targets related to spinal cord injury,including tumor protein p53(TP53),Myc proto-oncogene protein(MYC),and G1/S-specific cyclin-D1(CCND1).The 5 targets of caspase 3(CASP3)and JUN proto-oncogene protein(JUN)played an important role in the protein interaction network.The biological processes involved in the treatment of spinal cord injury by tanshinoneⅡA mainly include drug reaction,lipopolysaccharide reaction,and cell response to DNA damage stimulation;the molecular functions involved include enzyme binding,transcription factor binding,and protein binding.Its mechanism may be related to cAMP signaling pathway,MAPK signaling pathway,PI3 K-Akt signaling pathway,HIF-1 signaling pathway,TNF signaling pathway,apoptosis and other pathways.Conclusion:TanshinoneⅡA has multiple target and multi-channel effects in the treatment of spinal cord injury.It may interfere with the process of spinal cord injury by promoting neuronal survival,promoting axon regeneration,inhibiting neuronal apoptosis and anti-inflammatory.