摘要
目的:基于网络药理学和分子对接的方法探讨张氏腰痛方治疗腰椎间盘退变(LIDD)的分子生物学机制。方法:通过检索数据库,筛选张氏腰痛方的活性成分和作用靶点,以及LIDD的相关基因。通过R软件筛选张氏腰痛方治疗LIDD的共同靶基因,构建“药物-成分-靶点-疾病”网络以及共同靶基因的蛋白质相互作用网络,同时挖掘网络中潜在的蛋白质功能模块。关键靶基因进行GO功能富集分析与KEEG通路富集分析,以揭示这些靶基因的潜在生物学功能和通路。结果:共筛选出202个有效成分和164个共同靶基因,包括10个核心靶基因。富集分析结果表明,张氏腰痛方治疗LIDD的靶点主要作用于晚期糖基化终产物及其受体(AGE-RAGE)信号通路、肿瘤坏死因子(TNF)信号通路、细胞凋亡和低氧诱导因子-1(HIF-1)信号通路等。这些生物过程主要参与炎症反应、氧化应激和细胞凋亡的调控。分子对接结果显示,张氏腰痛方治疗LIDD的主要活性成分divaricatol、槲皮素、O-乙酰基哥伦比亚苷元、紫堇灵、黄芪紫檀烷苷与核心靶点TNF、AKT1、白细胞介素-6、TP53、血管内皮生长因子A具有良好的结合能力。结论:本研究初步证实了张氏腰痛方治疗LIDD具有“多成分、多靶点、多通路”的特点,主要从抗炎、抗氧化应激、抑制细胞凋亡和自噬等方面发挥对LIDD的治疗作用。
Objective:Based on network pharmacology and molecular docking methods,this study aims to explore the molecular biological mechanism of Zhang's Waist Pain Formula in the treatment of lumbar intervertebral disc degeneration(LIDD).Methods:By searching the database,the active ingredients and targets of Zhang's Waist Pain Formula,as well as the related genes of LIDD,were screened.Software R was used to screen common target genes of Zhang's Waist Pain Formula.A"drug-component-target-disease"network and a protein interaction network with common target genes were constructed,while exploring potential protein functional modules in the network.GO functional enrichment analysis and KEEG pathway enrichment analysis on key target genes were performed to reveal their potential biological functions and pathways.Results:A total of 202 active ingredients and 164 common target genes were screened,including 10 core target genes.The enrichment analysis results indicate that the targets of Zhang's Waist Pain Formula in treating LIDD mainly act on AGE-RAGE signaling pathway,TNF signaling pathway,cell apoptosis,and HIF-1 signaling pathway.These biological processes are mainly involved in the regulation of inflammatory response,oxidative stress,and cell apoptosis.The molecular docking results showed that the main active ingredients of Zhang's Waist Pain Formula for treating LIDD,including divaricatol,quercetin,O-acetylcolumbidin,corynoline,and Isomucronulatol 7-O-glucoside have good binding ability with core targets TNF,AKT1,interleukin-6,TP53,and vascular endothelial growth factor A.Conclusion:This study preliminarily confirms that Zhang's Waist Pain Formula has the characteristics of"multiple components,multiple targets,and multiple pathways"in the treatment of LIDD,mainly playing a therapeutic role in anti-inflammatory,antioxidant stress,inhibition of cell apoptosis,and autophagy.
作者
陈杨达豪
劳杨骏
徐彬
徐卫星
张树良
盛红枫
CHEN Yang-da-hao;LAO Yang-jun;XU Bin;XU Wei-xing;ZHANG Shu-liang;SHENG Hong-feng
出处
《风湿病与关节炎》
2024年第3期1-6,36,共7页
Rheumatism and Arthritis
基金
浙江省中医药科技计划项目(2023ZL305)
浙江省中医药科技计划项目(2023ZR073)
浙江省中医药传承与创新“十百千”人才工程(杏林工程)2019年省级名中医传承人项目(浙中医药[2019]16号)。
关键词
腰椎间盘退变
张氏腰痛方
网络药理学
靶点预测
分子对接
lumbar intervertebral disc degeneration
Zhang's Waist Pain Formula
network pharmacology
target prediction
molecular dockings
