{
  "abstract": "目的: 椎间盘退变(intervertebral disc degeneration，IVDD)是慢性下腰痛及多种脊柱退行性疾病的重要病理基础，环境污染物暴露可能是影响椎间盘稳态的潜在外源性因素。三氯生(triclosan，TCS)是一种广泛存在的环境抗菌污染物，其与IVDD之间的分子联系尚不明确。本研究旨在探讨TCS与IVDD之间的潜在分子联系，筛选TCS暴露相关IVDD的候选分子，并通过动物实验进行体内验证。\n\n方法: 从基因表达综合数据库(Gene Expression Omnibus，GEO)获取6个IVDD转录组数据集，其中GSE23130、GSE56081和GSE124272构成训练队列，GSE15227、GSE34095和GSE70362构成外部验证队列。采用替代变量分析(surrogate variable analysis，SVA)结合ComBat算法校正批次效应，利用Limma筛选IVDD差异表达基因。整合ChEMBL、PharmMapper和SwissTargetPrediction数据库预测TCS潜在作用靶点，筛选TCS与IVDD共同候选基因，并进行蛋白质相互作用网络、基因本体(Gene Ontology，GO)和京都基因与基因组数据库(Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析。采用10种机器学习算法及其组合建立127个预测模型，结合外部验证和Shapley加法解释(Shapley additive explanation，SHAP)分析筛选优先候选分子，并采用AutoDock Vina评价TCS与候选蛋白的潜在结合能力。在体内实验中，将8周龄C57BL/6J小鼠随机分为对照组和TCS暴露组，TCS暴露组经饲料口服给予200 mg TCS/kg饲料(200 ppm)，连续12周。采用显微CT测定腰椎L4/5平均椎间隙高度；采用Safranin O-Fast Green染色评价髓核细胞数量、椎间盘组织结构、蛋白聚糖染色情况及组织学退变评分；采用免疫组织化学染色和蛋白质印迹法检测椎间盘组织中花生四烯酸5-脂氧合酶(arachidonate 5-lipoxygenase，ALOX5)和过氧化物酶体增殖物激活受体δ(peroxisome proliferator-activated receptor delta，PPARD)的表达。\n\n结果: 共获得238个TCS候选靶点，并鉴定出HMGCR、PPARD、NR1H2、SEC14L2、FGFR1、ALOX5、LTA4H、ACSS2和NQO2共9个TCS-IVDD共同候选基因。富集分析显示，这些基因主要涉及脂质及类固醇代谢、花生四烯酸代谢和凋亡细胞清除。外部验证显示，PPARD、FGFR1和SEC14L2在IVDD组织中表达下调，而ALOX5、HMGCR、NR1H2、LTA4H和NQO2表达上调(均P<0.05)。SHAP分析显示，PPARD和ALOX5对模型预测具有较高贡献。分子对接显示，TCS与ALOX5、PPARD、FGFR1和HMGCR的最低结合能分别为-7.8、-7.2、-7.2和-6.1 kcal/mol。动物实验显示，与对照组相比，TCS组L4/5平均椎间隙高度显著降低[(272.32±18.89) μm vs (206.50±13.15) μm]，髓核细胞数显著减少(618.20±36.46 vs 377.20±23.37)，组织学退变评分显著升高(2.60±1.14 vs 12.20±1.48)(均P<0.001)。Safranin O-Fast Green染色显示TCS组髓核与纤维环边界模糊、组织结构紊乱及蛋白聚糖染色减弱。免疫组织化学显示，ALOX5阳性表达升高，PPARD阳性表达降低(均P<0.001)。蛋白质印迹法结果显示ALOX5相对表达量升高，PPARD相对表达量降低(均P<0.05)。\n\n结论: 在200 mg TCS/kg饲料、连续12周的挑战性饮食暴露条件下，TCS可诱导小鼠出现IVDD表型。PPARD降低和ALOX5升高与TCS暴露相关椎间盘病理改变具有一致性，提示脂质代谢及炎症脂质介质异常可能参与这一过程。PPARD和ALOX5可能是连接TCS暴露、脂质代谢紊乱和IVDD的关键候选分子。",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "安琪 蒋",
      "orcid": "0009-0002-2802-9166"
    },
    {
      "name": "柏力 覃"
    },
    {
      "name": "冠奇 李"
    },
    {
      "name": "杰灵 刘"
    },
    {
      "name": "Yousaf Muhammad"
    },
    {
      "name": "质钰 丁"
    },
    {
      "name": "凯强 孙"
    },
    {
      "name": "劲松 李",
      "orcid": "0000-0001-7649-0817"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fzqjmeykve69g.bib",
  "cited_by": 0,
  "doi": "10.11817/j.issn.1672-7347.2026.260413",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710917/",
  "id": "fzqjmeykve69g",
  "issns": [
    "1672-7347"
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  "landing_url": "https://doi.org/10.11817/j.issn.1672-7347.2026.260413",
  "language": "zh",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Articles"
    ],
    [
      "openalex",
      "2734|Spine and Intervertebral Disc Pathology"
    ]
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  "openalex": "W7223912228",
  "pdf_url": null,
  "pmcid": "PMC13710917",
  "pmid": "42935200",
  "published": "2026-08-28",
  "publisher": "Central South University",
  "ris": "https://research.draconitic.com/paper/fzqjmeykve69g.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:47Z",
      "native_id": "PMC13710917",
      "source": "pmc",
      "url": "https://doi.org/10.11817/j.issn.1672-7347.2026.260413"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Spine and Intervertebral Disc Pathology",
      "subfield": "general"
    }
  ],
  "title": "三氯生诱导椎间盘退变的关键分子靶点筛选与体内验证",
  "title_text": "三氯生诱导椎间盘退变的关键分子靶点筛选与体内验证",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:47Z",
  "url": "https://research.draconitic.com/paper/fzqjmeykve69g",
  "venue": "Journal of Central South University Medical Sciences",
  "versions": []
}