基于数据挖掘、网络药理学及分子对接技术分析中医药治疗腰椎术后疼痛的用药规律及作用机制

Analysis of the Mechanism of Action of Traditional Chinese Medicine in the Treatment of Postoperative Lumbar Pain Based on Data Mining， Network Pharmacology， and Molecular Docking Techniques

摘要:

目的：运用数据挖掘、网络药理学与分子对接技术，分析中医药治疗腰椎术后疼痛的用药规律，并预测其潜在的作用机制。方法：系统检索中英文数据库，纳入中药复方治疗腰椎术后疼痛的临床研究，提取证素、高频中药及处方配伍规律，整合核心药物组合。利用GeneCards、OMIM、TTD、PharmGKB数据库检索汇总疾病相关靶点，借助在线韦恩作图平台取药物疾病交集靶点。构建“中药-成分-靶点-疾病”网络及蛋白互作（PPI） 网络。对交集靶点进行基因本体（GO） 功能和京都基因与基因组百科全书（KEGG） 通路富集分析，并进行分子对接验证。结果：腰椎术后疼痛的核心病位为经络、肝、筋骨、肾，病性为气滞、血瘀，核心治法为活血化瘀，补气养血，补肝肾、强筋骨。高频中药有当归、甘草、黄芪、牛膝、川芎等；高频中药主要为活血化瘀药、补气药、补血药等；药性主要为温性，药味主要为甘味，主要归肝经。核心药物组合为鸡血藤、红花、甘草、当归、川芎、桃仁、黄芪、地龙、牛膝、桂枝、乳香。网络药理学筛选出核心药物组合的关键活性成分为黄芩素、豆甾醇、β-谷甾醇、槲皮素等，核心靶点为肿瘤蛋白p53 （TP53）、酪氨酸蛋白激酶Src（SRC）、信号转导与转录激活因子3（STAT3）、磷脂酰肌醇4，5-二磷酸3-激酶催化亚基α（PIK3CA）、磷脂酰肌醇3-激酶调节亚基1（PIK3R1） 等。KEGG分析结果主要涉及糖尿病并发症中的晚期糖基化终末产物-受体（AGE-RAGE）、丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇3激酶/蛋白激酶B （PI3K-Akt） 信号通路。分子对接结果显示关键活性成分与核心靶点的分子对接结合能均＜-5.0 kcal/mol。结论：中医药治疗腰椎术后疼痛遵循“活血化瘀、补虚通络”原则，核心药物组合可能通过多成分、多靶点调控炎症及神经痛相关通路发挥镇痛作用。

Abstract:

Abstract： Objective： To analyze the medication patterns of traditional Chinese medicine （TCM） in the treatment of postoperative lumbar pain and to predict its potential mechanisms of action by integrating data mining， network pharmacology， and molecular docking techniques. Methods： Chinese and English databases were systematically retrieved to identify clinical studies on Chinese medicine compounds for treating postoperative lumbar pain. Syndrome elements， high-frequency Chinese herbal medicines， and prescription compatibility patterns were extracted，and core herbal combinations were integrated. Disease-related targets were retrieved from The Human Gene Database （GeneCards），Online Mendelian Inheritance in Man （OMIM），Therapeutic Target Database （TTD），and Pharmacogenetics and Pharmacogenomics Knowledge Base （PharmGKB）， and the intersection of herbal targets and disease targets was obtained using an online Venn diagram platform. A "herbal-component-target-disease" network and a protein-protein interaction （PPI） network were constructed. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed on the intersecting targets， followed by molecular docking validation. Results： The core disease location of postoperative lumbar pain involved the meridians，liver，sinews and bones，and kidney，with the pathological characteristics being qi stagnation and blood stasis. The core therapeutic principles were activating blood and resolving stasis，tonifying qi and nourishing blood，and tonifying the liver and kidney to strengthen sinews and bones. The high-frequency herbs included Angelicae Sinensis Radix， Glycyrrhizae Radix et Rhizoma， Astragali Radix， Achyranthis Bidentatae Radix， and Chuanxiong Rhizoma. The high-frequency herbs were mainly blood-activating and stasis-resolving medicinals， qi-supplementing medicinals， and blood-tonifying medicinals； they were predominantly warm in nature， sweet in flavor， and mainly entered the liver meridian. The core herbal combination was composed of Spatholobi Caulis， Croci Stigma， Glycyrrhizae Radix et Rhizoma，Angelicae Sinensis Radix，Chuanxiong Rhizoma ，Persicae Semen，Astragali Radix， Pheretima， Achyranthis Bidentatae Radix， Cinnamomi Ramulus， and Olibanum. Network pharmacology screening identified the key active ingredients of the core herbal combination as baicalein，stigmasterol，β-sitosterol，quercetin， etc.， and the core targets as tumor protein p53 （TP53）， tyrosine-protein kinase Src （SRC）， signal transducer and activator of transcription 3 （STAT3） ， phosphatidylinositol 4， 5-bisphosphate 3-kinase catalytic subunit alpha （PIK3CA）， and phosphatidylinositol 3-kinase regulatory subunit 1 （PIK3R1）， among others. KEGG analysis mainly involved the advanced glycation end products-receptor for advanced glycation end products （AGE-RAGE） signaling pathway in diabetic complications，the mitogen-activated protein kinase （MAPK） signaling pathway，and the phosphatidylinositol 3-kinase/protein kinase B （PI3K-Akt） signaling pathway. Molecular docking results showed that the binding energies of all key active ingredients binding to core targets were < -5.0 kcal/mol. Conclusion： The treatment of postoperative lumbar pain with TCM follows a principle of "activating blood and resolving stasis，tonifying deficiency and unblocking collaterals. " The core herbal combination may exert analgesic effects by modulating inflammation and neuropathic pain-related pathways through multi-component and multi-target interactions.