小鼠心脏移植慢性排斥反应模型的建立和分析

Establishment and analysis of chronic rejection model of mouse heart transplantation

    摘要
  • 摘要:
    目的  建立小鼠心脏移植慢性排斥反应（CR）模型并分析其特点。
    方法 以异基因Balb/c和C57BL/6小鼠分别为供体和受体行心脏移植，于术后1、2 d给予腹腔注射细胞毒性T淋巴细胞相关抗原4免疫球蛋白（CTLA4-Ig）。观察移植物存活时间、供者特异性抗体（DSA）水平、移植物病理学表现和炎症细胞浸润情况。
    结果 异基因移植模型中，CTLA4-Ig治疗后移植物存活时间延长（28.2±4.1）d比（7.0±0.7）d，P＜0.01）；术后第2、3、4周血清DSA-IgG水平升高，DSA-IgM水平不变；术后3周移植心脏心肌细胞损伤、炎症细胞浸润、间质纤维化和毛细血管内C4d沉积，且术后第4周加重；移植物内浸润的免疫细胞主要为巨噬细胞、T细胞和浆细胞。
    结论 本研究利用小鼠异基因心脏移植加用CTLA4-Ig成功建立了CR模型，为后续CR的发病机制和干预研究提供基础。

     

    Abstract:
    Objective Establish a chronic rejection (CR) model of mouse heart transplantation and analyze its characteristics.
    Methods Allogeneic Balb/c and C57BL/6 mice were used as donor and recipient for heart transplantation, and intraperitoneal injection of cytotoxic T lymphocyte-associated antigen 4 immunoglobulin (CTLA4-Ig) was given 1 and 2 days after surgery. Graft survival time, donor specific antibody (DSA) level, graft pathology and inflammatory cell infiltration were observed.
    Results In allogeneic transplantation model, graft survival time was prolonged after CTLA4-Ig treatment (28.2±4.1) d vs. (7.0±0.7) d, P < 0.01. The level of serum DSA-IgG increased at 2, 3 and 4 weeks after surgery, while the level of DSA-IgM remained unchanged. Myocardial cell injury, inflammatory cell infiltration, interstitial fibrosis and C4d deposition in capillaries were aggravated 3 weeks after operation. And it worsened 4 weeks after operation. The infiltrated immune cells were mainly macrophages, T cells and plasma cells.
    Conclusions In this study, mouse allogeneic heart transplantation combined with CTLA4-Ig successfully established a CR model, which provided a basis for subsequent studies on the pathogenesis and intervention of CR.

     

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