西罗莫司对异种动脉补片移植后的免疫调节作用研究

Study of immunoregulatory effect of sirolimus on xenotransplantaion with arterial patch

    摘要
  • 摘要:
      目的  探讨西罗莫司在异种动脉补片移植中的免疫调节作用。
      方法  选择野生型巴马猪至食蟹猴异种动脉补片移植手术后14 d受体猴的外周血单核细胞（POD14）为研究对象。设置二甲基亚砜（DMSO）对照组（体积比为1︰1 000）和西罗莫司实验组（终浓度为0.1 μmol/L和0.5 μmol/L），分别培养1.0 d和5.5 d，检测POD14细胞活性；设置DMSO对照组和西罗莫司实验组（终浓度为0.1 μmol/L），培养5.5 d，检测POD14细胞中T、B细胞的数量并检测细胞因子含量和信使核糖核酸（mRNA）表达水平。
      结果  与DMSO对照组比较，终浓度为0.1 μmol/L和0.5 μmol/L的西罗莫司处理1.0 d后，POD14细胞活性降低（ P < 0.01~0.001）；终浓度为0.1 μmol/L和0.5 μmol/L的西罗莫司处理POD14细胞5.5 d后，POD14细胞活性均明显降低（均为 P < 0.001）。与DMSO对照组比较，西罗莫司（终浓度0.1 μmol/L）降低POD14细胞中CD3+CD4+ T细胞和CD3+CD8+ T细胞的数量（ P < 0.05~0.01），而CD3-CD20+B细胞数量略有升高（ P < 0.01）。与DMSO对照组比较，西罗莫司实验组的细胞因子干扰素（IFN）-γ、白细胞介素（IL）-2、IL-4、IL-5和IL-6含量均明显降低（ P < 0.05~0.001）；西罗莫司降低细胞因子IFN-γ、肿瘤坏死因子（TNF）-α、IL-2、IL-4、IL-5和IL-6的mRNA表达水平（ P < 0.05~0.001）。
      结论  西罗莫司抑制异种动脉补片移植术后受体猴POD14细胞的增殖，主要机制是降低T细胞数量和抑制免疫排斥相关细胞因子的表达和分泌。

     

    Abstract:
      Objective  To investigate the immunoregulatory effect of sirolimus on the xenotransplantation with arterial patch.
      Methods  The xenotransplantation of arterial grafts was taken from the wild-type Bama pigs to cynomolgus monkeys. The peripheral blood mononuclear cells of recipient monkeys at 14 days after xenotransplantation (POD14) were selected as subjects. Dimethyl sulphoxide (DMSO) was used in the control group (volume ratio of 1:1 000) and sirolimus was administered in the sirolimus experimental group (final concentration of 0.1 μmol/L and 0.5 μmol/L). The cells were cultured for 1.0 and 5.5 d, respectively. The activity of POD14 cells was evaluated. The DMSO control and sirolimus experimental groups (final concentration of 0.1 μmol/L) were established and cultured for 5.5 d. The quantity of T and B cells in POD14 cells was counted and the expression levels of cytokines and messenger RNA (mRNA) were quantitatively measured.
      Results  Compared with the DMSO control group, the activity of POD14 cells was significantly decreased after sirolimus treatment at a final concentration of 0.1 and 0.5 μmol/L for 1.0 d ( P < 0.01-0.001). After sirolimus treatment at a final concentration of 0.1 and 0.5 μmol/L for 5.5 d, the activity of POD14 cells was significantly decreased (both P < 0.001). Compared with the DMSO control group, the quantity of CD3+CD4+ T cells and CD3+CD8+T cells in POD14 cells was significantly reduced after sirolimus treatment at a final concentration 0.1 μmol/L ( P < 0.05-0.01), whereas the quantity of CD3-CD20+B cells was considerably elevated ( P < 0.01). Compared with DMSO control group, the levels of interferon(IFN)-γ, interleukin(IL)-2, IL-4, IL-5 and IL-6 in the sirolimus experimental group were significantly down-regulated ( P < 0.05-0.001). The expression levels of IFN-γ, tumor necrosis factor(TNF)-α, IL-2, IL-4, IL-5 and IL-6 mRNA were significantly down-regulated ( P < 0.05-0.001).
      Conclusions   Sirolimus inhibits the proliferation of POD14 cells in the recipient monkeys after xenotransplantation with arterial patch. The underlying mechanism is that the sirolimus can reduce the quantity of T cells and suppress the expression and secretion of immune rejection-related cytokines.

     

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