目的 基于网络药理学探讨并分析筒鞘蛇菰（Balanophora involucrata Hook. f.，BIH）治疗肝损伤的作用及分子机制，并通过大鼠体内实验验证相关预测靶点及筒鞘蛇菰提取物-蛇菰多糖（Polysaccharides of Balanophora involucrata Hook. f.，BPS）对实验性肝损伤的保护作用。方法 化学专业数据库、TCMID和TCMSP平台检索筒鞘蛇菰组成的化合物及可能靶点，以肝损伤为关键词检索GeneCards和网站，获得相关靶点，绘制Venn图，选交集靶点，将“化合物-靶点和疾病-靶点”关系导入Cytoscape V3.7.2软件，获得化合物-靶点-疾病的三重网络，对化合物及相关靶点蛋白行分子对接，并用交集靶点绘制蛋白互作网络图及进行GO生物功能和KEGG信号途径富集分析。结果 筒鞘蛇菰主要成分有11个化合物，其中与肝损伤有37个交集靶点，高度关联靶点包括NOS3、ESR1、TNF、MAOA、PTGS2、IL10等，GO和KEGG富集分析发现筒鞘蛇菰治疗肝损伤的分子机制，可能与调节肾上腺素能信号通路、cGMP-PKG信号及神经活性配体-受体交互通路等有关，而且ADRA1B、ADRA2A、ADRA2C、ADRB1/2等基因高度富集于这些通路中。动物体内实验发现BPS灌胃处理可减轻肝组织损伤、调控血清炎症因子肿瘤坏死因子α（Tumor necrosis factor， TNF-α）和白细胞介素10（IL-10）水平、提高抗氧化酶超氧化物歧化酶（superoxide dismutase，SOD）活性，并增强肝组织内氧化应激相关蛋白核因子E2相关因子2（NF-E2-related factor 2，NRF2）和醌NADH脱氢酶1（NQO1）的表达，从而抑制大鼠体内氧化应激损伤、减轻炎症反应和细胞凋亡，达到保护实验性肝损伤的作用。结论 本研究初步确定筒鞘蛇菰治疗肝损伤的有效成分、“化合物-蛋白-靶点”关联网络及发挥作用的分子机制，并通过动物体内实验证实蛇菰多糖保护肝损伤的机制与上调NRF2/NQO1通路来减轻氧化应激反应性损伤、减轻肝细胞凋亡有关。

Objective To explore and analyze the effect and molecular mechanism of Balanophora involucrata Hook. f. (BIH) on liver injury based on network pharmacology and further to determine the protective effects of the Polysaccharides of BIH (BPS) on experimental liver injury in rats in vivo according to the relative predicted targets.Methods The compounds and possible targets of BIH on liver injury were obtained in Chemistry database with liver damage and corresponding diseases as the key words in GeneCards and OMIM websites. Venn diagram was drawn to get the intersection targets, and the relationship of ‘compound-targets and disease-targets’ were imported into the software of Cytoscape V3.7.2 to get the triple network. The molecular docking between the compound and the target protein was carried out, and the protein-protein interaction network was plotted with the intersection targets, then the GO biological function and KEGG signal pathway enrichment analysis were carried out.Results BIH contained 11 compounds, including 37 intersection targets with liver damage. The high associated targets included NOS3, ESR1, TNF, MAOA, PTGS2, IL10 and so on. GO and KEGG enrichment analysis showed that the molecular mechanisms of BIH on liver injury might be related to regulating adrenergic signal pathway, cGMP-PKG signal and neural activity of ligand receptor interaction pathways and so on, and ADRA1B, ADRA2A, ADRA2C and ADRB1/2 genes were highly enriched in these pathways. The results showed that BPS can reduce liver tissue injury and cell apoptosis, regulate the levels of inflammatory factors TNF-α and IL-10 in serum, increase the activity of antioxidant enzyme SOD, and enhance the expression of NRF2 and NQO1 proteins in liver tissue, so as to inhibit oxidative stress injury, reduce inflammation and apoptosis, and achieve the protective effects of experimental liver injury in rats.Conclusion The study preliminarily identified the active components, ‘compound-protein-target’ association network and the molecular mechanism of its effect. The in vivo experiments in animals confirmed that the mechanism of BIH polysaccharide protection against liver injury was related to the up-regulation of NRF2/NQO1 pathway to reduce oxidative stress reactive injury and hepatocyte apoptosis.

湖北省教育厅科学研究计划指导性项目（B2020361）：基于Nrf2/ARE通路探讨蛇菰多糖对酒精性肝损伤的保护作用及机制，负责人：朱耀乾。