小鼠颈部异位心脏移植急性排斥反应模型中的动态免疫学特征

Dynamic immunological characteristics in acute rejection model of cervical heterotopic heart transplantation in mice

  • 摘要:
    目的  建立小鼠颈部心脏移植急性排斥模型,评估移植后生存情况及排斥反应的动态过程。
    方法  将小鼠随机分为假手术组(n=10)、同系移植组(n=21)和同种异体移植组(n=65),分别进行假手术、同系颈部心脏移植、同种异体颈部心脏移植。观察受体小鼠及移植物存活情况、移植物组织病理学变化、脾淋巴细胞亚群和血清、移植物炎症因子表达情况。
    结果  假手术组、同系移植组术后7 d生存率及移植物存活率为100%;同种异体移植组5例手术失败,均于术后1 d死亡,术后7 d生存率为86%,存活的小鼠移植物均于术后7 d停止搏动。同种异体移植组在术后7 d出现明显排斥反应,伴随组织损伤和CD8+T细胞浸润;脾脏CD8+T细胞比例在术后持续升高,而CD4+T细胞比例呈下降趋势;血清和移植物干扰素-γ表达在术后5 d达到峰值,而肿瘤坏死因子-α表达差异无统计学意义。
    结论  小鼠心脏移植急性排斥反应在术后5~7 d加剧,此时可能是免疫干预的关键时间窗口。

     

    Abstract:
    Objective To establish an acute rejection model of cervical heart transplantation in mice and evaluate the survival and dynamic rejection process post-transplantation.
    Methods Mice were randomly divided into sham operation group (n=10), syngeneic transplantation group (n=21), and allogeneic transplantation group (n=65). Sham operation, syngeneic cervical heart transplantation, and allogeneic cervical heart transplantation were performed respectively. The survival of recipient mice and grafts, histopathological changes of graft tissues, subpopulations of splenic lymphocytes, and expression of inflammatory factors in serum and grafts were observed.
    Results The survival rate and graft survival rate of the sham operation group and syngeneic transplantation group were 100% at 7 days after surgery. In the allogeneic transplantation group, 5 cases failed and died on the first day after surgery. The survival rate at 7 days after surgery was 86%, and all surviving mice had grafts that stopped beating at 7 days after surgery. The allogeneic transplantation group showed significant rejection at 7 days after surgery, accompanied by tissue damage and CD8+ T cell infiltration. The proportion of CD8+ T cells in the spleen continued to rise post-operation, while the proportion of CD4+ T cells showed a downward trend. The expression of interferon-γ in serum and grafts peaked at 5 days after surgery, while the expression of tumor necrosis factor-α showed no statistical significance.
    Conclusions Acute rejection following heart transplantation in mice intensifies between 5 to 7 days after surgery, which may be a critical time window for immunological intervention.

     

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