基于网络药理学探讨针刺治疗肝肾亏虚型腰椎间盘突出症的选穴规律、作用机制及其与调身通痹方的靶点对比分析

Acupoint Selection Rules and Mechanisms of Acupuncture in Treating Liver-Kidney Deficiency Type Lumbar Disc Herniation and Comparative Target Analysis Between Acupuncture and Tiaoshen Tongbi Formula Based on Network Pharmacology

摘要

目的 探讨针刺治疗肝肾亏虚型腰椎间盘突出症（lumbar disc herniation，LDH）的选穴规律及潜在作用机制；运用网络药理学筛选其核心靶点及信号通路，并与调身通痹方进行对比分析，比较两者作用靶点与通路的异同并探讨潜在协同基础。方法 系统检索中英文数据库并设定纳入、排除标准；汇总针刺高频穴位、归经与配伍规律，采用 Apriori 算法进行关联规则分析。根据纳入机制研究提取并标准化高频穴位相关候选靶点；结合人类疾病基因数据库（Disease Gene Network Database，DisGeNET）、人类基因整合数据库（GeneCards Database）、在线人类孟德尔遗传数据库（Online Mendelian Inheritance in Man，OMIM）获得 LDH 相关靶点；构建“穴位-靶点-疾病”网络，进行拓扑分析及蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络分析；采用 Benjamini-Hochberg 校正，以错误发现率（false discovery rate，FDR）< 0.05 为标准开展基因本体（Gene Ontology，GO）功能富集及京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集。整合调身通痹方成分-靶点数据，利用 Venn 图与网络图比较共同靶点与特异靶点；同时回顾性纳入临床病例进行补充性描述验证。结果 纳入文献 126 篇（样本量 4 128 例）；回顾性病例 203 例（来自上海中医药大学附属龙华医院天山分院）。共识别 11 个高频穴位，主要归属足太阳膀胱经、督脉；基于 Apriori 算法获得多组高支持度、置信度和提升度的配伍，整体呈局部与远端、补益与通络相结合的特点。网络药理学锁定白细胞介素-6、肿瘤坏死因子（tumor necrosis factor，TNF）-α、核因子 κB （nuclear factor κB，NF-κB）等关键靶点；富集通路主要涉及 TNF、NF-κB、Toll 样受体（Toll-like receptor，TLR）及 NOD 样受体（NOD-like receptor，NLR）等，FDR < 0.05。针刺与调身通痹方比较显示，两者在炎症、氧化应激与免疫调控上存在重叠靶点，同时各具特异方向，提示可能存在共同调控与机制互补；临床病例治疗后视觉模拟量表（Visual Analogue Scale，VAS）评分下降，日本骨科协会（Japanese Orthopaedic Association，JOA）评分升高。结论 针刺治疗肝肾亏虚型 LDH 具有明确的选穴与经络规律，其作用可能涉及多靶点、多通路调控。调身通痹方与针刺在部分靶点和通路上存在重叠并呈机制互补，为后续开展针药联合的实验与临床研究提供依据。

Abstract

Objective To elucidate the acupoint selection patterns and potential mechanisms of acupuncture treatment for lumbar disc herniation (LDH) of the liver-kidney deficiency type. Using network pharmacology, we screened its core targets and signaling pathways and compared it with the Tiaoshen Tongbi Formula to compare their target and pathway profiles and explore a potential mechanistic basis for synergy. Methods A systematic search of Chinese and English databases was conducted, and inclusion and exclusion criteria were set. High-frequency acupoints, meridian attribution and compatibility rules were summarized, and association rule analysis was performed using the Apriori algorithm. Candidate targets related to high-frequency acupoints were extracted and standardized from the included mechanistic studies; LDH-related targets were obtained by combining the Disease Gene Network Database (DisGeNET), GeneCards Database and Online Mendelian Inheritance in Man (OMIM). An "acupoint-target-disease" network was constructed, and topological analysis and protein-protein interaction (PPI) network analysis were performed. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out with Benjamini-Hochberg correction, using false discovery rate (FDR) < 0.05 as the threshold. Component-target data of the Tiaoshen Tongbi Formula were integrated, and shared and specific targets were compared using Venn diagrams and network diagrams. Meanwhile, clinical cases were retrospectively enrolled for supplementary descriptive validation. Results A total of 126 articles (4 128 cases) were included, along with 203 retrospective cases (from the Tianshan Branch, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine). Eleven high-frequency acupoints were identified, primarily belonging to the Foot-Taiyang Bladder Meridian and the Governor Vessel. Analysis based on Apriori algorithm yielded multiple compatibility combinations with high support, confidence and lift, showing an overall pattern that combined local with distal selection and tonification with channel-unblocking. Network pharmacology identified key targets such as interleukin-6, tumor necrosis factor (TNF)-α and nuclear factor κB (NF-κB); enriched pathways mainly involved TNF, NF-κB, Toll-like receptor (TLR) and NOD-like receptor (NLR) signaling, with FDR < 0.05. Comparison between acupuncture and the Tiaoshen Tongbi Formula revealed overlapping targets in inflammation, oxidative stress and immune regulation, while each had specific action directions, suggesting shared regulation and mechanistic complementarity. In the clinical cases, Visual Analogue Scale (VAS) scores decreased and Japanese Orthopaedic Association (JOA) scores increased after treatment. Conclusion Acupuncture treatment for liver-kidney deficiency type LDH has clear rules of acupoint selection and meridian distribution, and its effects may involve multi-target and multi-pathway regulation. The Tiaoshen Tongbi Formula and acupuncture show partial overlap in targets and pathways together with mechanistic complementarity, providing a rationale for further experimental and clinical studies of combined acupuncture-herbal treatment.

关键词

网络药理学 / 针刺 / 调身通痹方 / 肝肾亏虚 / 腰椎间盘突出症 / 作用靶点 / 分子机制

Key words

network pharmacology / acupuncture / Tiaoshen Tongbi Formula / liver-kidney deficiency / lumbar disc herniation / therapeutic target / molecular mechanism

参考文献

[1] 周金苹, 冉家杰, 田航, 等. 气滞血瘀型腰椎间盘突出症的中医外治法研究进展[J].护理学, 2023, 12(3): 375-380.

[2] Zhang A S, Xu A, Ansari K,et al. Lumbar disc herniation: diagnosis and management[J].Am J Med, 2023, 136(7): 645-651.

[3] Gao Q, Yang H, Masood U,et al. Lumbar disc herniation with contralateral symptoms: a case-series of 11 patients and literature review[J].Orthop Surg, 2023, 15(11): 2839-2847.

[4] Gong G, Yan Z, Lai Q,et al. Inflammation preservation strategy: reconciling pain control and disc resorption in lumbar disc herniation[J].Front Immunol, 2025, 16: 1653681.

[5] 黄庆, 刘静, 冯丽. 针刺治疗腰椎间盘突出症疗效观察[J].天津中医药大学学报, 2026, 45(1): 18-26.

[6] 鄢驰恒, 冯大刚, 段宇辰, 等. 杵针治疗腰椎间盘突出症的研究进展[J].临床医学进展, 2025, 15(1): 845-850.

[7] 许萌, 张超, 李嘉玮, 等. 传统针刺对腰椎间盘突出症效应影响的Meta分析[J].四川中医, 2025, 43(4): 189-202.

[8] 王爰爰, 崔露. 电针治疗联合其他疗法治疗腰椎间盘突出症的研究进展[J].中医学, 2025, 14(1): 334-340.

[9] 潘渴, 邝涛. 中医药治疗腰椎间盘突出症研究进展[J].江苏中医药, 2023, 55(8): 75-79.

[10] 中华医学会骨科学分会脊柱外科学组, 中华医学会骨科学分会骨科康复学组. 腰椎间盘突出症诊疗指南[J].中华骨科杂志, 2020, 40(8): 477-487.

[11] 国家中医药管理局. 中医病证诊断疗效标准: ZY/T 001.1～001.9-94[S].南京: 南京大学出版社, 1994.

[12] 吴文玉, 詹少锋, 焦欣, 等. 中医药领域机器学习研究的现状与发展趋势探讨[J].中华中医药学刊, 2026, 44(2): 11-16, 263-264.

[13] 周翀, 黄春玲, 王静, 等. 针刺治疗儿童抽动障碍临床选穴及配穴规律[J].辽宁中医杂志, 2026, 53(5): 161-166.

[14] 张玉钱, 金泽. 针刺治疗腰椎间盘突出症的应用进展及临床研究方法学质量: 现状、问题与改进策略[J].临床医学进展, 2026, 16(1): 2890-2896.

[15] 李文芳, 董孟炜, 靳海珠, 等. 针刺调控干细胞增殖和分化的机制[J].中国组织工程研究, 2026, 30(19): 5050-5056.

[16] 项瑞瑞, 郭雅雯, 李小花, 等. 身痛逐瘀汤联合针刺治疗寒凝血瘀型腰椎间盘突出症疗效观察[J].河北中医, 2025, 47(2): 233-236.

[17] 武宁, 严骏, 李标鹏, 等. 痹痛方联合针刺治疗腰椎间盘突出症肝肾亏虚型临床观察[J].实用中医药杂志, 2025, 41(7): 1351-1354.

[18] Wang Y, Zhou Y, Tian H,et al. NF-κB signalling pathway in neurodegenerative diseases: acupuncture as a potential therapeutic approach[J].Brain Res, 2025, 1865: 149893.

基金资助

国家中医优势专科建设项目(2025YC-ZJK)

上海市卫生健康委员会“十四五”中医特色专科项目(ZYTSZK1-2)

上海市长宁区卫生健康委员会科研项目(20234Z011)

上海市长宁区卫生健康委员会科研项目(20234Z009)

上海市长宁区卫生健康委员会青年课题(2022QN11)

上海市长宁区卫生健康委员会天山中医医院PI团队建设项目(PI202426)