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

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

  • 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。

     

    Abstract:
      Objective  To investigate the effect of human umbilical cord mesenchymal stem cells (HUC-MSCs) on CD4+ T cells in liver after hepatic ischemia-reperfusion injury (HIRI) in mice.
      Methods  Two hundred and twentyfive mice were randomly divided into sham group, control group and MSC group, with 75 mice in each group. HIRI model mice were used in MSC group and control group. HUC-MSCs were injected in MSC group through inferior vena cava. Normal saline was injected in control group through inferior vena cava. Only laparotomy and abdominal closure were performed in sham group without blood vessel clipping. At 6, 12 and 24 h after operation, 15 mice of each group were randomly selected to sample eyeball blood and liver tissues, and the 30 mice left in each group were used to extract intrahepatic mononuclear cells. The number of intrahepatic mononuclear cells, percentage, number and positive rate of CD4+ T cells in the mice of various groups at different time points were compared. The content of interleukin (IL)-17 in serum and liver tissue as well as expression levels of costimulatory molecules B7-1 and B7-2 messenger RNA (mRNA) in liver tissues of the mice at different time points were compared.
      Results  At 12 and 24 h after operation, the number of intrahepatic mononuclear cells of control group was significantly higher than that of sham group, while the number of intrahepatic mononuclear cells of MSC group was significantly lower than that of control group (P < 0.01-0.05). At 6, 12 and 24 h after operation, the percentage, number and positive rate of CD4+T cells of control group were significantly higher than those of sham group (all P < 0.01), while the percentage of CD4+T cells of MSC group was significantly lower than that of control group (P < 0.01-0.05). At 12 and 24 h after operation, the number and positive rate of CD4+ T cells of MSC group were significantly lower than those of control group (P < 0.01-0.05). At 6, 12 and 24 h after operation, the IL-17 contents in serum and liver tissues of control group were higher than those of sham group (all P < 0.01), while the IL-17 contents in serum and liver tissues of MSC group were lower than those of control group (all P < 0.01). At 6 h after operation, the mRNA expression level of B7-2 of control group was higher than that of sham group (P < 0.05). At 12 and 24 h after operation, the mRNA expression levels of B7-1 and B7-2 of control group were higher than those of sham group (all P < 0.01), while the mRNA expression levels of B7-1 and B7-2 of MSC group were lower than those of control group (all P < 0.01).
      Conclusions  HUC-MSCs inhibits the number of CD4+T cells and the secretion of IL-17 in liver after HIRI, as well as decreases the number of intrahepatic mononuclear cells and the mRNA expression of B7-1 and B7-2, thereby alleviating HIRI.

     

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