目的 运用网络药理学和分子对接技术探讨鸡骨草多糖治疗对乙酰氨基酚致肝损伤的靶点和作用机制。方法 检索文献获得鸡骨草多糖的主要成分；通过中医药分子机制生物信息学分析工具（BATMAN）、Swiss Target Prediction、中药系统药理学数据库和分析平台（TCMSP）、毒性与基因比较数据库（CTD）、Gene Cards以及HERB数据库获取鸡骨草多糖的潜在作用靶点；利用Gene Cards、人类孟德尔遗传数据库（OMIM）获取疾病靶点；将疾病靶点与鸡骨草多糖作用靶点取交集，获取共有靶点；通过STRING数据库和Cytoscape_v3.10.3软件构建蛋白相互作用（PPI）网络和“药物–成分–靶点–疾病”网络；DAVID在线平台对核心靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析；运用CB-DOCK2在线对接平台进行分子对接验证。结果 鸡骨草多糖的主要化学成分为鼠李糖、阿拉伯糖、半乳糖和葡萄糖，作用靶点有6 838个，对乙酰氨基酚致肝损伤靶点827个，共有靶点为588个，获得白蛋白（ALB）、肿瘤坏死因子（TNF）、肿瘤蛋白53（TP53）、基质金属蛋白酶9（MMP9）、胱天蛋白酶3（CASP3）和B细胞淋巴瘤2（Bcl-2）等10个核心靶点。GO显示鸡骨草多糖治疗对乙酰氨基酚致肝损伤主要涉及在凋亡过程的负调控和对外源物质刺激的反应等生物过程，细胞外空间和细胞外区域等细胞组分，以及相同的蛋白结合和酶结合等分子功能。KEGG通路分析涉及为脂质与动脉粥样硬化、乙型肝炎、癌症通路、细胞凋亡、丙型肝炎、磷脂酰肌醇3激酶–蛋白激酶B（PI3K-Akt）信号通路、晚期糖基化终产物及其受体（AGE-RAGE）、Janus激酶（JAK）-信号传导及转录激活蛋白（STAT）信号通路、叉头框蛋白O（Fox O）信号通路和p53信号通路等；分子对接结果显示半乳糖和葡萄糖与排名前10的核心靶点均有较好的对接效果，其中与MMP9对接效果最好。结论 鸡骨草多糖可能通过ALB、TNF、TP53、MMP9、CASP3、BCL2等靶点，作用于多条信号通路，缓解对乙酰氨基酚致肝损伤。

Objective To investigate the targets and mechanism of Abrus cantoniensis polysaccharides in treatment of acetaminophen-induced liver injury using network pharmacology and molecular docking. Methods The main components of A. cantoniensis polysaccharides were obtained from the literature; Potential targets of A. cantoniensis polysaccharides were retrieved from the BATMAN, Swiss Target Prediction, TCMSP, CTD, Gene Cards, and HERB databases; Disease targets were acquired from the Gene Cards and OMIM databases; The disease targets and the action targets of A. cantoniensis polysaccharides were intersected to obtain common targets; A protein-protein interaction (PPI) network and a “drug-component-target-disease” network were constructed using the STRING database and Cytoscape_v3.10.3 software; DAVID online platform performs GO and KEGG enrichment analysis on core targets; Molecular docking validation was performed using the CB-DOCK2 online docking platform. Results The main chemical components of A. cantoniensis polysaccharides were rhamnose, arabinose, galactose, and glucose. There were 6 838 targets, 827 targets of acetaminophen-induced liver injury, and 588 common targets. Ten core targets such as ALB, TNF, TP53, MMP9, CASP3 and BCL2 were obtained. GO showed that the treatment of acetaminophen-induced liver injury by A. cantoniensis polysaccharide mainly involved biological processes such as negative regulation of apoptotic process and response to xenobiotic stimulus, cellular components such as extracellular space and extracellular region, as well as molecular functions such as identical protein binding and enzyme binding. KEGG pathway analysis involved lipid and atherosclerosis, hepatitis B, pathways in cancer, apoptosis, hepatitis C, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway in diabetic complications, JAK-STAT signaling pathway, FoxO signaling pathway and p53 signaling pathway. The molecular docking results indicated that both galactose and glucose exhibited favorable docking affinities with all of the top 10 core targets, with the most effective docking observed with MMP9. Conclusion A. cantoniensis polysaccharides may alleviate liver injury by targeting key molecules such as ALB, TNF, TP53, MMP9, CASP3, BCL2, and acting through multiple signaling pathways to alleviate acetaminophen-induced liver injury.

R286.7

广西壮族自治区卫生和计划生育委员会自筹经费科研课题（Z20180110）；桂林医学院中青年教职工科研能力提升项目（2018glmcy098）