留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

人脐带间充质干细胞对小鼠肝缺血-再灌注损伤后肝内CD4+T细胞的影响

周朝荣 吕海金 孙瑶 安玉玲 范明明 易慧敏

周朝荣, 吕海金, 孙瑶, 等. 人脐带间充质干细胞对小鼠肝缺血-再灌注损伤后肝内CD4+T细胞的影响[J]. 器官移植, 2018, 9(2): 103-109. doi: 10.3969/j.issn.1674-7445.2018.02.003
引用本文: 周朝荣, 吕海金, 孙瑶, 等. 人脐带间充质干细胞对小鼠肝缺血-再灌注损伤后肝内CD4+T细胞的影响[J]. 器官移植, 2018, 9(2): 103-109. doi: 10.3969/j.issn.1674-7445.2018.02.003
Zhou Chaorong, Lyu Haijin, Sun Yao, et al. Effect of human umbilical cord mesenchymal stem cells on CD4+ T cells in liver after hepatic ischemia-reperfusion injury in mice[J]. ORGAN TRANSPLANTATION, 2018, 9(2): 103-109. doi: 10.3969/j.issn.1674-7445.2018.02.003
Citation: Zhou Chaorong, Lyu Haijin, Sun Yao, et al. Effect of human umbilical cord mesenchymal stem cells on CD4+ T cells in liver after hepatic ischemia-reperfusion injury in mice[J]. ORGAN TRANSPLANTATION, 2018, 9(2): 103-109. doi: 10.3969/j.issn.1674-7445.2018.02.003

人脐带间充质干细胞对小鼠肝缺血-再灌注损伤后肝内CD4+T细胞的影响

doi: 10.3969/j.issn.1674-7445.2018.02.003
基金项目: 

广东省科技计划项目 2014A020211010

详细信息
    作者简介:

    周朝荣,男,1989年生,硕士研究生,研究方向为干细胞治疗,Email: zhouchr3@hotmail.com

    通讯作者:

    易慧敏,女,1975年生,博士,主任医师,研究方向为干细胞治疗,Email: ylhmin@hotmail.com

  • 中图分类号: R617

Effect of human umbilical cord mesenchymal stem cells on CD4+ T cells in liver after hepatic ischemia-reperfusion injury in mice

More Information
  • 摘要:   目的  探讨人脐带间充质干细胞(HUC-MSCs)对小鼠肝缺血-再灌注损伤(HIRI)后肝内CD4+T细胞的影响。  方法  将225只小鼠随机分为sham组、control组和MSC组,每组75只。其中MSC组和control组均为HIRI模型小鼠,MSC组通过下腔静脉注射HUC-MSCs,control组通过下腔静脉注射生理盐水,sham组仅进行开腹、关腹等操作,不行血管夹闭。分别于术后6、12、24 h,每组随机取15只小鼠,用于眼球取血法采血及取肝组织样本,每组剩下的30只小鼠用于肝内单核细胞的提取。比较各组小鼠不同时间点肝内单核细胞数量,CD4+T细胞比例、数量和阳性率;比较各组小鼠不同时间点血清和肝组织中白细胞介素(IL)-17含量,及肝组织内共刺激分子B7-1和B7-2信使核糖核酸(mRNA)表达水平。  结果  术后12、24 h,control组的肝内单核细胞数量明显高于sham组,而MSC组的肝内单核细胞数量明显低于control组(P < 0.01~0.05)。术后6、12、24 h,control组的CD4+T细胞比例、数量及阳性率均明显高于sham组(均为P < 0.01),MSC组的CD4+T细胞比例明显低于control组(P < 0.01~0.05);术后12、24 h,MSC组的CD4+T细胞数量和阳性率均明显低于control组(P < 0.01~0.05)。术后6、12、24 h,control组血清和肝组织中的IL-17含量均高于sham组(均为P < 0.01),而MSC组血清和肝组织中的IL-17含量均低于control组(均为P < 0.01)。术后6 h,control组B7-2的mRNA表达水平高于sham组(P < 0.05);术后12、24 h,control组B7-1和B7-2的mRNA表达水平均高于sham组(均为P < 0.01),而MSC组B7-1和B7-2的mRNA表达水平均低于control组(均为P < 0.01)。  结论  HUC-MSCs抑制HIRI后肝内CD4+T细胞的数量和IL-17的分泌,同时减少肝内单核细胞数量及B7-1和B7-2 mRNA表达,减轻HIRI。

     

  • 图  1  3组小鼠肝内单核细胞和CD4+T细胞的数量和比例

    A图为3组小鼠肝内CD4+T细胞的流式细胞图;B图为3组小鼠肝脏单核细胞数量的比较;C图为3组小鼠CD4+T细胞比例的比较;D组为3组小鼠CD4+T细胞数量的比较;与sham组比较,aP<0.01;与control组比较,bP<0.05,cP<0.01

    Figure  1.  The counts and ratio of monocytes and CD4+ T cells in liver of mice of three groups

    图  2  3组小鼠肝内CD4+ T细胞的阳性率

    A图为3组小鼠肝内CD4+T细胞的免疫组化图片(×200),箭头所示为CD4+T细胞;B图为3组小鼠CD4+T细胞阳性率的比较,与sham组比较,aP<0.01;与control组比较,bP<0.05,cP<0.01

    Figure  2.  The positive rate of CD4+ T cells in liver of mice of three groups

    图  3  3组小鼠血清和肝组织中IL-17含量的比较

    与sham组比较,aP<0.01;与control组比较,bP<0.01

    Figure  3.  Comparison of the content of IL-17 in serum and liver tissue of mice among three groups

    图  4  3组小鼠肝组织中B7-1和B7-2 mRNA表达水平的比较

    A图为3组小鼠肝组织中B7-1 mRNA表达水平的比较;B图为3组小鼠肝组织中B7-2 mRNA表达水平的比较;与sham组比较,aP<0.01,bP<0.05;与control组比较,cP<0.01

    Figure  4.  Comparison of the expression levels of B7-1 and B7-2 mRNA in liver tissue of mice among three groups

  • [1] CALDWELL CC, TSCHOEP J, LENTSCH AB, et al. Lymphocyte function during hepatic ischemia/reperfusion injury[J]. J Leukoc Biol, 2007, 82(3): 457-464. doi: 10.1189/jlb.0107062
    [2] SHEN X, WANG Y, GAO F, et al. CD4 T cells promote tissue inflammation via CD40 signaling without de novo activation in a murine model of liver ischemia/reperfusion injury[J]. Hepatology, 2009, 50(5): 1537-1546. DOI: 10.1002/hep.23153.
    [3] CALDWELL CC, OKAYA T, MARTIGNONI A, et al. Divergent functions of CD4+ T lymphocytes in acute liver inflammation and injury after ischemia-reperfusion[J]. Am J Physiol Gastrointest Liver Physiol, 2005, 289(5): G969-G976. doi: 10.1152/ajpgi.00223.2005
    [4] REIFART J, RENTSCH M, MENDE K, et al. Modulating CD4+ T cell migration in the postischemic liver: hepatic stellate cells as new therapeutic target?[J]. Transplantation, 2015, 99(1): 41-47. DOI: 10.1097/TP.0000000000000461.
    [5] MAGGI U, FORNONI G, CENTONZE L, et al. Ischemia time and liver transplantation, today[J]. Transplant Proc, 2014, 46(7): 2295-2299. DOI: 10.1016/j.transproceed.2014.07.040.
    [6] HAGA H, YAN IK, BORRELLI DA, et al. Extracellular vesicles from bone marrow-derived mesenchymal stem cells protect against murine hepatic ischemia/reperfusion injury[J]. Liver Transpl, 2017, 23(6): 791-803. DOI: 10.1002/lt.24770.
    [7] ROWART P, ERPICUM P, DETRY O, et al. Mesenchymal stromal cell therapy in ischemia/reperfusion injury[J]. J Immunol Res, 2015: 602597. DOI: 10.1155/2015/602597.
    [8] UCHIDA Y, FREITAS MC, ZHAO D, et al. The protective function of neutrophil elastase inhibitor in liver ischemia/reperfusion injury[J]. Transplantation, 2010, 89(9): 1050-1056. DOI: 10.1097/TP.0b013e3181d45a98.
    [9] VAN GOLEN RF, REINIERS MJ, VRISEKOOP N, et al. The mechanisms and physiological relevance of glycocalyx degradation in hepatic ischemia/reperfusion injury[J]. Antioxid Redox Signal, 2014, 21(7): 1098-1118. DOI: 10.1089/ars.2013.5751.
    [10] ZWACKA RM, ZHANG Y, HALLDORSON J, et al. CD4(+) T-lymphocytes mediate ischemia/reperfusion-induced inflammatory responses in mouse liver[J]. J Clin Invest, 1997, 100(2): 279-289. doi: 10.1172/JCI119533
    [11] YAO Z, PAINTER SL, FANSLOW WC, et al. Human IL-17: a novel cytokine derived from T cells[J]. J Immunol, 1995, 155(12): 5483-5486. http://www.jimmunol.org/content/155/12/5483.full.pdf
    [12] KONO H, FUJⅡ H, OGIKU M, et al. Role of IL-17A in neutrophil recruitment and hepatic injury after warm ischemia-reperfusion mice[J]. J Immunol, 2011, 187(9): 4818-4825. DOI: 10.4049/jimmunol.1100490.
    [13] KOJIMA N, SATO M, SUZUKI A, et al. Enhanced expression of B7-1, B7-2, and intercellular adhesion molecule 1 in sinusoidal endothelial cells by warm ischemia/reperfusion injury in rat liver[J]. Hepatology, 2001, 34(4 Pt 1): 751-757. doi: 10.1053/jhep.2001.27804?scrollTo=references
    [14] TAKADA M, CHANDRAKER A, NADEAU KC, et al. The role of the B7 costimulatory pathway in experimental cold ischemia/reperfusion injury[J]. J Clin Invest, 1997, 100(5): 1199-1203. doi: 10.1172/JCI119632
    [15] LENTSCH AB. Regulatory mechanisms of injury and repair after hepatic ischemia/reperfusion[J]. Scientifica (Cairo), 2012: 513192. DOI: 10.6064/2012/513192.
    [16] FEISST V, BROOKS AE, CHEN CJ, et al. Characterization of mesenchymal progenitor cell populations directly derived from human dermis[J]. Stem Cells Dev, 2014, 23(6): 631-642. DOI: 10.1089/scd.2013.0207.
    [17] 徐土炳, 李莉, 罗兴迪, 等.骨髓间充质干细胞在肝细胞损伤恢复中的作用[J].实用医学杂志, 2017, 33(5): 687-692. DOI: 10.3969/j.issn.1006-5725.2017.05.004.

    XU TB, LI L, LUO XD, et al. Role of bone marrow mesenchymal stem cells in recovery process of hepatocyte injury[J]. J Pract Med, 2017, 33(5): 687-692. DOI: 10.3969/j.issn.1006-5725.2017.05.004.
    [18] ROSSIGNOL J, BOYER C, THINARD R, et al. Mesenchymal stem cells induce a weak immune response in the rat striatum after allo or xenotransplantation[J]. J Cell Mol Med, 2009, 13(8B): 2547-2558. DOI: 10.1111/j.1582-4934.2009.00657.x.
    [19] 唐飞龙, 栾佐, 吴南海, 等.脐带间充质干细胞治疗儿童移植相关并发症的疗效观察[J].转化医学杂志, 2017, 6(3): 132-136. DOI: 10.3969/j.issn.2095-3097.2017.03.002.

    TANG FL, LUAN Z, WU NH, et al. Therapeutic effect of umbilical cord-mesenchymal stem cell on transplantation-related complications in children[J]. Translat Med J, 2017, 6(3): 132-136. DOI: 10.3969/j.issn.2095-3097.2017.03.002.
    [20] BLOOM DD, CENTANNI JM, BHATIA N, et al. A reproducible immunopotency assay to measure mesenchymal stromal cell-mediated T-cell suppression[J]. Cytotherapy, 2015, 17(2): 140-151. DOI: 10.1016/j.jcyt.2014.10.002.
    [21] DANCHUK S, YLOSTALO JH, HOSSAIN F, et al. Human multipotent stromal cells attenuate lipopolysaccharide-induced acute lung injury in mice via secretion of tumor necrosis factor-α-induced protein 6[J]. Stem Cell Res Ther, 2011, 2(3): 27. DOI: 10.1186/scrt68.
    [22] HSU WT, LIN CH, CHIANG BL, et al. Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10+IFN-γ+CD4+ regulatory T cells to control transplant arteriosclerosis[J]. J Immunol, 2013, 190(5): 2372-2380. DOI: 10.4049/jimmunol.1202996.
  • 加载中
图(4)
计量
  • 文章访问数:  80
  • HTML全文浏览量:  17
  • PDF下载量:  9
  • 被引次数: 0
出版历程
  • 收稿日期:  2017-12-20
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2018-03-15

目录

    /

    返回文章
    返回