Immutol诱导大鼠心脏移植物免疫耐受的研究

Immutol induces immune tolerance of cardiac grafts in rat models

    摘要
  • 摘要:
      目的  探讨Immutol诱导大鼠心脏移植物产生免疫耐受的作用。
      方法  建立大鼠腹腔异位心脏移植模型。将受体大鼠分成5组：空白对照组（n=6）；DMSO组（n=6），使用二甲基亚砜(DMSO)给药至移植物停搏；Immutol组（n=6），使用Immutol给药至移植物停搏；环孢素（CsA）组（n=10），使用CsA给药20 d后停药；联合实验组（n=13），使用Immutol给药60 d后停药，CsA给药20 d后停药。观察各组大鼠心脏移植物的存活时间和病理学变化；检测各组大鼠血清白细胞介素（IL）-10、干扰素（IFN）- γ的含量，以及心脏组织的吲哚胺2, 3-双加氧酶（IDO）、纤维蛋白原样蛋白2（Fgl2）的信使核糖核酸（mRNA）表达情况。
      结果  联合实验组心脏移植物可长期存活，存活时间>180 d，均可诱导产生免疫耐受。联合实验组术后39 d心脏移植物的病理评分明显低于CsA组（P < 0.05）。联合实验组术后9、39 d血清IL-10和IFN- γ含量均明显高于CsA组（均为P < 0.05），联合实验组IL-10和IFN- γ含量随时间延长逐渐升高。联合实验组术后39 d IDO和Fgl2 mRNA表达量明显高于CsA组（均为P < 0.05），联合实验组术后IDO的mRNA表达量呈现逐渐升高的趋势。联合实验组术后180 d Fgl2的mRNA表达量明显高于术后9、39 d（均为P < 0.05）。
      结论  Immutol联合CsA可有效抑制急性排斥反应发生，停药后可诱导移植物长期存活，产生免疫耐受。

     

    Abstract:
      Objective  To investigate the effect of Immutol on inducing the immune tolerance of cardiac grafts in rat models.
      Methods  A rat model of heterotopic abdominal heart transplantation was established. The recipient rats were divided into 5 groups: blank control group (n=6); dimethyl sulfoxide (DMSO) group (n=6), in which DMSO was administered until the cardiac graft arrest; Immutol group (n=6), in which Immutol was administered until the cardiac graft arrest; ciclosporin (CsA) group (n=10), in which CsA was administered for 20 d; combined group (n=13), in which Immutol was given for 60 d combined with CsA for 20 d. The survival time and pathological changes of cardiac grafts in each group were observed. The contents of serum interleukin (IL)-10 and interferon (IFN)-γ were detected. The expression levels of indoleamine 2, 3-dioxygenase (IDO) and fibrinogen-like protein 2(Fgl2) messenger RNA(mRNA) in heart tissues of rats in each group were measured.
      Results  In the combined group, the cardiac grafts survived for >180 d and immune tolerance was induced. The pathological score of cardiac grafts in the combined group was significantly lower than that in the CsA group at postoperative 39 d (P < 0.05). The levels of serum IL-10 and IFN-γ in the combined group were significantly higher than those in the CsA group at 9 d and 39 d after operation (both P < 0.05). The content of serum IL-10 and IFN-γ in the combined group were gradually increased over time. At postoperative 39 d, the expression levels of IDO and Fgl2 mRNA in the combined group were significantly higher than those in the CsA group (both P < 0.05). The expression level of IDO mRNA in the combined group tended to gradually elevate after operation. In the combined group, the expression level of Fgl2 mRNA at postoperative 180 d was significantly higher than those at 9 d and 39 d after operation (both P < 0.05).
      Conclusions  Combined administration of Immutol and CsA can effectively inhibit the incidence of acute rejection, and maintain the long-term survival of the cardiac grafts and induce immune tolerance after drug withdrawal.

     

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