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粪菌移植对脓毒症小鼠肠道T细胞免疫稳态和肠道炎症的作用

徐嘉若 关伟 何婉雪 徐建桥 解立新

徐嘉若, 关伟, 何婉雪, 徐建桥, 解立新. 粪菌移植对脓毒症小鼠肠道T细胞免疫稳态和肠道炎症的作用[J]. 解放军医学院学报, 2023, 44(6): 662-667. doi: 10.3969/j.issn.2095-5227.2023.06.015
引用本文: 徐嘉若, 关伟, 何婉雪, 徐建桥, 解立新. 粪菌移植对脓毒症小鼠肠道T细胞免疫稳态和肠道炎症的作用[J]. 解放军医学院学报, 2023, 44(6): 662-667. doi: 10.3969/j.issn.2095-5227.2023.06.015
XU Jiaruo, GUAN Wei, HE Wanxue, XU Jianqiao, XIE Lixin. Effect of fecal bacteria transplantation on immune state of intestinal T cell and intestinal inflammation in septic mice[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2023, 44(6): 662-667. doi: 10.3969/j.issn.2095-5227.2023.06.015
Citation: XU Jiaruo, GUAN Wei, HE Wanxue, XU Jianqiao, XIE Lixin. Effect of fecal bacteria transplantation on immune state of intestinal T cell and intestinal inflammation in septic mice[J]. ACADEMIC JOURNAL OF CHINESE PLA MEDICAL SCHOOL, 2023, 44(6): 662-667. doi: 10.3969/j.issn.2095-5227.2023.06.015

粪菌移植对脓毒症小鼠肠道T细胞免疫稳态和肠道炎症的作用

doi: 10.3969/j.issn.2095-5227.2023.06.015
基金项目: 首都卫生发展科研专项项目(首发2022-1-5091)
详细信息
    作者简介:

    徐嘉若,女,在读硕士,医师。研究方向:呼吸与危重症,微生态与宿主免疫。Email: xjiaruo@126.com

    通讯作者:

    解立新,男,博士,主任医师,教授,解放军总医院呼吸与危重症医学部主任。Email: xielx301@126.com

  • 中图分类号: R631;R392.12;R456

Effect of fecal bacteria transplantation on immune state of intestinal T cell and intestinal inflammation in septic mice

More Information
  • 摘要:   背景  脓毒症是重症患者的主要死亡原因,目前缺乏有效的治疗手段,近年来粪菌移植(fecal microbiota transplantation,FMT)治疗脓毒症受到越来越多关注。  目的  探讨粪菌移植治疗的免疫学机制,明确粪菌移植治疗对脓毒症小鼠肠道T细胞免疫状态和功能以及肠道炎症状态的影响,为临床治疗提供理论依据。  方法  8 ~ 10周龄C57BL/6小鼠随机分为对照组、脓毒症组和粪菌移植组,后两组通过腹腔注射脂多糖构建脓毒症小鼠模型,粪菌移植组小鼠在脂多糖注射24 h后以灌胃的方式接受来自健康小鼠的粪菌移植,检测各组小鼠肠道固有层T细胞及其亚群以及表面功能性分子的表达,测量结肠长度,检测小肠和结肠组织的病理改变。  结果  相比对照组小鼠,脓毒症组小鼠小肠T淋巴细胞显著减少(22.03% ± 1.50% vs 30.78% ± 1.62%,P < 0.01),其中CD4+ T细胞(15.08% ± 1.01% vs 21.58% ± 1.95%,P < 0.01)和CD8+ T细胞(5.05% ± 0.39% vs 6.28% ± 0.21%,P < 0.01)均显著减少,小肠CD4+ T细胞(227.25 ± 11.47 vs 266.00 ± 6.27,P < 0.01)和CD8 + T细胞(73.40 ± 6.82 vs 102.80 ± 4.80,P < 0.01)表面CD28的表达显著下调,CD8+ T细胞表面PD-1的表达(19.90 ± 1.47 vs 15.00 ± 2.25,P < 0.05)显著上调,差异均有统计学意义,说明脓毒症小鼠肠道T细胞的数量和功能受到抑制,结肠长度显著缩短[(6.90 ± 0.08) cm vs (8.18 ± 0.22) cm,P < 0.01],组织病理结果显示小肠和结肠均出现明显的炎症和损伤;而与脓毒症组小鼠相比,粪菌移植组小鼠肠道T细胞(26.43% ± 1.86% vs 22.03% ± 1.50%,P < 0.05),包括CD4+ T细胞(17.48 ± 0.85% vs 15.08% ± 1.01%,P < 0.05)和CD8+ T细胞(6.74% ± 0.39% vs 5.05% ± 0.39%,P < 0.01)数量均出现回升,CD4+ T细胞(252.25 ± 7.14 vs 227.25 ± 11.47,P < 0.05)和CD8+ T细胞(95.30 ± 3.63 vs 73.40 ± 6.82,P < 0.01)表面CD28的表达出现回升,CD8+ T细胞表面PD-1的表达(17.10 ± 0.52 vs 19.90 ± 1.47,P < 0.05)出现回降,差异均有统计学意义,提示经粪菌移植治疗的脓毒症小鼠肠道T细胞的数量和功能得到一定恢复,结肠长度明显恢复[(8.13 ± 0.26) cm vs (6.90 ± 0.08) cm,P < 0.01],组织病理结果显示小肠和结肠的炎症和损伤得到了明显的缓解。  结论  经粪菌移植治疗的脓毒症小鼠肠道T细胞数量和功能得到部分恢复,肠道T细胞的免疫稳态得到一定程度的恢复,并且显著缓解了脓毒症小鼠肠道的炎症和损伤。

     

  • 图  1  各组小鼠结肠长度比较(n=4)

    Figure  1.  Colon length of mice in different groups (n=4)

    图  2  经与未经粪菌移植治疗的脓毒症小鼠结肠组织病理学改变(HE染色,标尺=200 μm)

    Figure  2.  Representative images of colon tissues sections in septic mice with or without FMT treatment (HE staining, scale bar=200 μm)

    图  3  经与未经粪菌移植治疗的脓毒症小鼠小肠组织病理学改变(HE染色,比例尺=200 μm)

    Figure  3.  Representative images of small intestine tissues sections in septic mice with or without FMT treatment (HE staining, scale bar=200 μm)

    图  4  各组小鼠小肠固有层T细胞及其亚群数量变化(n=4)

    Figure  4.  Relative numbers of T cells, CD4 + T cells and CD8 + T cells in lamina propria of small intestine in each group (n=4)

    图  5  各组小鼠小肠固有层T细胞表面CD28和PD-1表达情况(n=4)

    Figure  5.  Expression of CD28 and PD-1 on CD4 + T cells and CD8 + T cells in lamina propria of small intestine in each group (n=4)

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出版历程
  • 收稿日期:  2022-11-21
  • 网络出版日期:  2023-04-14
  • 刊出日期:  2023-06-28

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