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巨噬细胞在小肠移植急性排斥反应期的极化状态及意义

骆阳, 徐兴伟, 嵇武. 巨噬细胞在小肠移植急性排斥反应期的极化状态及意义[J]. 器官移植, 2023, 14(6): 817-823. doi: 10.3969/j.issn.1674-7445.2023129
引用本文: 骆阳, 徐兴伟, 嵇武. 巨噬细胞在小肠移植急性排斥反应期的极化状态及意义[J]. 器官移植, 2023, 14(6): 817-823. doi: 10.3969/j.issn.1674-7445.2023129
Luo Yang, Xu Xingwei, Ji Wu. Polarization state and significance of macrophage in acute rejection after intestinal transplantation[J]. ORGAN TRANSPLANTATION, 2023, 14(6): 817-823. doi: 10.3969/j.issn.1674-7445.2023129
Citation: Luo Yang, Xu Xingwei, Ji Wu. Polarization state and significance of macrophage in acute rejection after intestinal transplantation[J]. ORGAN TRANSPLANTATION, 2023, 14(6): 817-823. doi: 10.3969/j.issn.1674-7445.2023129

巨噬细胞在小肠移植急性排斥反应期的极化状态及意义

doi: 10.3969/j.issn.1674-7445.2023129
基金项目: 国家自然科学基金青年基金(81900598)
详细信息
    作者简介:
    通讯作者:

    嵇武(ORCID:0000-0002-6058-2888),教授,博士研究生导师,主任医师,研究方向为普通外科基础与临床研究,Email: jiwuvip@hotmail.com

  • 中图分类号: R617,R392.12

Polarization state and significance of macrophage in acute rejection after intestinal transplantation

More Information
  • 摘要:   目的  探究小肠移植术后发生急性排斥反应(AR)时巨噬细胞极化状态的改变。  方法  将6只Brown Norway(BN)大鼠和24只Lewis大鼠分为假手术组(6只Lewis大鼠)、同基因组(Lewis→Lewis,供受体各6只)和异基因组(BN→Lewis,供受体各6只)。对各组大鼠术后7 d的移植肠组织进行苏木素-伊红(HE)染色和脱氧核糖核酸末端转移酶介导的 dUTP 缺口末端标记(TUNEL)法检测,观察其病理学表现和细胞凋亡情况;采用酶联免疫吸附试验(ELISA)检测血清中M1和M2型巨噬细胞极化相关细胞因子表达水平;利用免疫荧光技术检测各组移植肠组织中M1和M2型巨噬细胞表面标志物并进行共定位计数分析。  结果  HE染色和TUNEL检测结果显示假手术组与同基因组肠上皮形态结构正常,未见明显凋亡小体;异基因组大鼠术后7 d移植肠组织上皮层绒毛结构破坏严重,隐窝数量减少,凋亡小体增多,炎症细胞浸润肠壁全层,呈现中-重度AR。ELISA结果显示异基因组受体鼠血清中M1型巨噬细胞极化相关细胞因子肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ和白细胞介素(IL)-12表达水平高于假手术组和同基因组,同基因组中M2型巨噬细胞极化相关细胞因子IL-10和转化生长因子(TGF)-β表达水平高于假手术组和异基因组,差异均有统计学意义(均为P<0.05)。免疫荧光结果显示异基因组移植肠组织中M1型巨噬细胞计数多于假手术组和同基因组,同基因组M2型巨噬细胞计数多于假手术组和异基因组,差异均有统计学意义(均为P<0.05)。  结论  小肠移植术后发生AR的移植物中,大量巨噬细胞浸润肠壁全层,以M1型为主并分泌大量促炎因子,调控巨噬细胞极化方向是治疗小肠移植术后AR的潜在方法。

     

  • 图  1  各组移植肠组织病理学表现(HE,×100)

    Figure  1.  Pathological findings of intestinal grafts in each group

    图  2  各组移植肠组织荧光染色及凋亡细胞计数

    注:A图为凋亡细胞荧光染色(×100);B图为凋亡细胞计数,与假手术组比较,aP<0.05,与同基因组比较,bP<0.05。

    Figure  2.  Fluorescence staining and apoptotic cell count in intestinal grafts of each group

    图  3  各组移植肠组织M1、M2型巨噬细胞免疫荧光共定位(免疫荧光,×100)

    注:A图为免疫荧光双标定位检测M1型巨噬细胞表面标志物F4/80、CD11b;B图为免疫荧光双标定位检测M2型巨噬细胞表面标志物F4/80、CD206。

    Figure  3.  Immunofluorescence co-localization of M1 and M2 type macrophages in intestinal grafts of each group

    图  4  各组移植肠组织M1型和M2型巨噬细胞计数

    注:图为各组移植肠组织中M1型和M2型巨噬细胞在100倍视野下计数;与假手术组比较,aP<0.05,与同基因组比较,bP<0.05。

    Figure  4.  Counts of M1 and M2 type macrophages in intestinal grafts of each group

    表  1  各组血清中M1型与M2型巨噬细胞极化相关细胞因子表达水平($\bar {\boldsymbol{x}} $±s,pg/mL)

    Table  1.   Expression levels of M1 and M2 macrophage polarization related cytokines in serum of each group

    组别nTNF-αIFN-γIL-12IL-10TGF-β
    假手术组 6 89.3±2.5 47.4±5.0 10.3±0.6 23. 8±1.0 97.7±4.8
    同基因组 6 97.9±6.1 50.0±2.1 11.1±1.2 45.8±1.9a 147.1±19.2a
    异基因组 6 213.8±4.1a,b 102.4±3.3 a,b 22.1±1.3 a,b 36.6±2.1b 74.6±3.6b
    F 1 456.16 432.27 234.97 246.95 60.99
      注:与假手术组比较,aP<0.05,与同基因组比较,bP<0.05。
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出版历程
  • 收稿日期:  2023-07-04
  • 录用日期:  2023-08-11
  • 网络出版日期:  2023-08-23
  • 刊出日期:  2023-11-09

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