{
  "abstract": "目的: 结核病目前仍是单一传染病致死的首要原因，现有疫苗的保护效果有限，仍有待研发安全且高效的新型结核病疫苗。超声联合酶解法制备的结核分枝杆菌B/R融合菌株灭活全菌裂解液(inactivated whole-cell lysate of Mycobacterium tuberculosis B/R fusion strain prepared by combined ultrasonic disruption and enzymatic digestion，UK-B/R)在确保菌体灭活完全的同时保留了关键抗原组分，但目前对其安全性及免疫原性的认识尚不充分。本研究旨在评价UK-B/R的安全性及其诱导的体液免疫应答。\n\n方法: 将小鼠单核巨噬细胞白血病细胞系RAW264.7分为空白对照(control)组、卡介苗(Bacillus Calmette-Guérin，BCG)组、结核分枝杆菌B/R融合菌株(B/R)组及UK-B/R组，各组分别干预细胞24 h后，采用酶联免疫吸附试验(enzyme-linked immunosorbent assay，ELISA)检测细胞培养上清液中白细胞介素-1β(interleukin-1β，IL-1β)和白细胞介素-6(interleukin-6，IL-6)的水平，并用流式细胞术检测细胞凋亡率。将6~8周龄C57BL/6J小鼠随机分为磷酸盐缓冲液(phosphate-buffered saline，PBS)组、BCG组、B/R组、UK-B/R组，分别进行急性毒性实验和长期毒性实验。在急性毒性实验中，各组小鼠单次皮下给药后连续观察14 d，记录小鼠一般状态、体重变化及死亡情况等。在长期毒性实验中，各组小鼠分别于第0、14、28天进行皮下免疫，于末次免疫后的第3天(急性期)和第14天(恢复期)收集血清和肺、肝、脾、肾组织，分别计算脏器指数，检测丙氨酸氨基转移酶(alanine aminotransferase，ALT)、天冬氨酸氨基转移酶(aspartate aminotransferase，AST)、白蛋白(albumin，ALB)、血肌酐(serum creatinine，SCr)和血尿素氮(blood urea nitrogen，BUN)水平，采用苏木精-伊红染色观察重要脏器的组织病理变化。另取6~8周龄C57BL/6J雌性小鼠15只随机分为PBS组、BCG组及UK-B/R组，在末次皮下免疫后的第14天，采用ELISA检测血清及支气管肺泡灌洗液(bronchoalveolar lavage fluid，BALF)中抗原特异性抗体水平。\n\n结果: UK-B/R组细胞培养上清液中IL-1β和IL-6水平均显著高于control组(均P<0.05)，其中IL-1β水平与BCG组及B/R组的差异均无统计学意义(均P>0.05)，IL-6水平明显低于BCG组及B/R组(均P<0.05)。UK-B/R组的细胞凋亡率与control组之间的差异无统计学意义(P>0.05)。急性毒性实验结果显示，各组小鼠均未出现异常反应，无死亡发生，体重均呈现增长的趋势且组间差异无统计学意义(P>0.05)。长期毒性实验结果显示，各组小鼠脏器指数(肺、肝、脾、肾)，以及ALT、AST、ALB、SCr及BUN水平之间的差异均无统计学意义(均P>0.05)；组织病理学检查显示各组小鼠肺、肝、脾、肾组织均未见明显病理改变。免疫学评价结果显示，UK-B/R组血清中特异性IgG抗体水平显著高于PBS组和BCG组；BALF中特异性IgG抗体和IgA抗体水平均较PBS组和BCG组显著升高(均P<0.05)。\n\n结论: UK-B/R在细胞及动物层面均表现出良好的安全性，且可诱导抗原特异性体液免疫与黏膜免疫应答。",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "智敏 盘",
      "orcid": "0009-0004-0844-4308"
    },
    {
      "name": "治勋 刘"
    },
    {
      "name": "粟 梁"
    },
    {
      "name": "晓梅 李"
    },
    {
      "name": "喜玲 邓"
    },
    {
      "name": "江涛 董"
    },
    {
      "name": "杰 张"
    },
    {
      "name": "小玲 柳"
    },
    {
      "name": "乐 章"
    },
    {
      "name": "芳 吴",
      "orcid": "0009-0003-3429-0130"
    },
    {
      "name": "万江 张",
      "orcid": "0000-0002-0294-473X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/03gs5r7sbx4nx.bib",
  "cited_by": 0,
  "doi": "10.11817/j.issn.1672-7347.2026.260001",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710881/",
  "id": "03gs5r7sbx4nx",
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  "landing_url": "https://doi.org/10.11817/j.issn.1672-7347.2026.260001",
  "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/",
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      "openalex",
      "2725|Tuberculosis Research and Epidemiology"
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  "openalex": "W7223824726",
  "pdf_url": null,
  "pmcid": "PMC13710881",
  "pmid": "42935198",
  "published": "2026-08-28",
  "publisher": "Central South University",
  "ris": "https://research.draconitic.com/paper/03gs5r7sbx4nx.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:45Z",
      "native_id": "PMC13710881",
      "source": "pmc",
      "url": "https://doi.org/10.11817/j.issn.1672-7347.2026.260001"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|Tuberculosis Research and Epidemiology",
      "subfield": "infectious-disease"
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  ],
  "title": "超声联合酶解法制备的结核分枝杆菌B/R融合菌株灭活全菌裂解液的安全性及其体液免疫应答",
  "title_text": "超声联合酶解法制备的结核分枝杆菌B/R融合菌株灭活全菌裂解液的安全性及其体液免疫应答",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:45Z",
  "url": "https://research.draconitic.com/paper/03gs5r7sbx4nx",
  "venue": "Journal of Central South University Medical Sciences",
  "versions": []
}