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MiR-155在大鼠肝移植术后排斥反应中作用机制的研究

李坤 孔伟浩 张俊斌 陈强星 孙翀 尹东亮 李慧 张剑

李坤, 孔伟浩, 张俊斌, 等. MiR-155在大鼠肝移植术后排斥反应中作用机制的研究[J]. 器官移植, 2018, 9(3): 194-199. doi: 10.3969/j.issn.1674-7445.2018.03.005
引用本文: 李坤, 孔伟浩, 张俊斌, 等. MiR-155在大鼠肝移植术后排斥反应中作用机制的研究[J]. 器官移植, 2018, 9(3): 194-199. doi: 10.3969/j.issn.1674-7445.2018.03.005
Li Kun, Kong Weihao, Zhang Junbin, et al. Study of miR-155 in the mechanism of rejection after liver transplantation in rats[J]. ORGAN TRANSPLANTATION, 2018, 9(3): 194-199. doi: 10.3969/j.issn.1674-7445.2018.03.005
Citation: Li Kun, Kong Weihao, Zhang Junbin, et al. Study of miR-155 in the mechanism of rejection after liver transplantation in rats[J]. ORGAN TRANSPLANTATION, 2018, 9(3): 194-199. doi: 10.3969/j.issn.1674-7445.2018.03.005

MiR-155在大鼠肝移植术后排斥反应中作用机制的研究

doi: 10.3969/j.issn.1674-7445.2018.03.005
基金项目: 

广东省科技计划项目 2014A020212159

广州市科学研究专项项目 2060404

详细信息
    作者简介:

    李坤,男,1993年生,硕士,住院医师,研究方向为肝脏肿瘤、肝脏移植,Email:likun0708@163.com

    通讯作者:

    张剑,男,1967年生,博士,教授,主任医师,研究方向为肝脏肿瘤、肝脏移植,Email:zhangjian629@sina.com

  • 中图分类号: R617, R318.04

Study of miR-155 in the mechanism of rejection after liver transplantation in rats

More Information
  • 摘要:   目的  探讨微小核糖核酸(miRNA,miR)-155在大鼠肝移植术后排斥反应中的作用机制。  方法  将大鼠分为异系移植模型组(排斥组,n=10),供体为雄性Lewis大鼠,受体为雄性BN大鼠;同系移植模型组(对照组,n=10),供、受体均为雄性Lewis大鼠;两组均按照“二袖套法”建立大鼠原位肝移植模型。术后第7日处死大鼠取血标本和肝组织。检测肝功能指标丙氨酸转氨酶(ALT)、总胆红素(TB)以及细胞因子白细胞介素(IL)-2、IL-4、干扰素(IFN)-γ的水平;光学显微镜下观察肝组织的病理变化情况。对两组大鼠肝组织样本每组选取3例进行高通量测序,检测排斥反应相关miRNA,进行生物信息学分析,预测并分析其相关的信号通路以及基因。  结果  肝功能检测显示排斥组大鼠血清中ALT、TB水平均高于对照组,差异均有统计学意义(均为 P < 0.01)。外周血细胞因子检测显示,与对照组比较,排斥组的IL-2和IFN-γ水平升高(均为 P < 0.01),IL-4水平下降( P < 0.01)。病理检查结果提示,与对照组比较,排斥组发生了明显的排斥反应。高通量检测结果示排斥组miR-155表达上调明显,为对照组5.89倍。生物信息学分析提示,miR-155的上调表达与哺乳动物雷帕霉素靶蛋白(mTOR)、丝裂原活化蛋白激酶(MAPK)及T细胞受体信号通路有关,可能参与调节的基因有酵母自噬基因(ATG1)及其同源基因ULK2、胰岛素样生长因子-1(Igf-1)以及G蛋白偶联受体的调节基因(Arrb1)等。  结论  miR-155可能促进了大鼠肝移植术后排斥反应的发生发展,涉及此过程的信号通路可能有mTOR、MAPK信号通路及T细胞受体信号途径,ATG1ULK2Igf-1以及Arrb1等基因可能参与了此过程。

     

  • 图  1  两组大鼠肝移植术后7 d肝组织病理学图片(HE,×200)

    A图为排斥组;B图为对照组

    Figure  1.  Histopathological pictures of liver tissue of rats in two groups at 7 d after liver transplantation

    图  2  大鼠肝组织miRNA表达聚类分析图

    红色为miRNA高表达,绿色为miRNA低表达,rno为大鼠

    Figure  2.  Cluster analysis picture of miRNA expression in liver tissue of rats

    表  1  两组大鼠肝移植术后7 d肝功能和细胞因子水平的比较

    Table  1.   Comparison of liver function and cytokine levels of rats between two groups at 7 d after liver transplantation((x±s))

    指标 排斥组(n=10) 对照组(n=10) t P
    ALT(U/L) 289±40 64±16 16.37 < 0.01
    TB(μmol/L) 26.1±5.3 4.9±1.6 12.11 < 0.01
    IL-2(ng/L) 331±23 58±17 30.43 < 0.01
    IL-4(ng/L) 088±24 231±170 24.67 < 0.01
    IFN-γ(ng/L) 302±25 50±19 25.24 < 0.01
    下载: 导出CSV

    表  2  大鼠肝移植术后发生排斥反应中表达差异变化的miRNA

    Table  2.   The miRNA with differential changes during rejection after liver transplantation in rats

    miRNA名称 FC( P < 0.05)
      表达上调
       rno-miR-155 5.89
       rno-miR-146b 5.52
       rno-miR-151 5.21
       rno-miR-130b 4.87
       rno-miR-140 4.78
       rno-miR-223 4.59
       rno-miR-101b 4.58
       rno-miR-342-3p 4.37
       rno-miR-128 4.24
       rno-miR-674-5p 4.02
       rno-miR-107 3.93
       rno-miR-132 3.88
       rno-miR-365 3.73
       rno-miR-142-3p 3.71
       rno-miR-16 3.23
       rno-miR-7a 3.17
       rno-miR-328 2.96
       rno-miR-146a 2.73
       rno-miR-15b 2.54
       rno-miR-93 2.45
       rno-miR-25 2.21
       rno-miR-150 2.07
       rno-miR-652 1.87
       rno-miR-99b* 1.73
       rno-miR-186 1.67
      表达下调
       rno-miR-194 0.05
       rno-miR-375 0.05
       rno-miR-31 0.06
       rno-miR-30c 0.09
       rno-miR-3752 0.11
       rno-miR-668 0.14
       rno-miR-505 0.15
       rno-miR-210 0.19
       rno-miR-490 0.21
       rno-miR-193 0.24
       rno-miR-122* 0.27
       rno-miR-291a-5p 0.28
       rno-miR-345-5p 0.31
       rno-miR-874 0.36
       rno-miR-434-3p 0.39
       rno-miR-10b 0.40
       rno-miR-22* 0.42
       rno-miR-872* 0.49
       rno-miR-802 0.53
       rno-miR-338* 0.55
       rno-miR-347 0.61
      rno为大鼠
    下载: 导出CSV
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出版历程
  • 收稿日期:  2018-02-18
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2018-05-15

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