肝硬化大鼠原位肝移植模型的制作及术后排斥反应的观察

Establishment of orthotopic liver transplantation model in cirrhosis rats and observation of postoperative of allografts rejection

目的制备肝硬化大鼠的原位肝移植模型，观察术后排斥反应发生情况，为进行其它研究创建一个平台。方法以皮下注射CCl4联合饮用苯巴比妥钠和乙醇溶液的方法制备大鼠肝硬化模型，应用改良的“二袖套”法建立大鼠原位肝移植模型，同系移植者的供、受者均为SD大鼠（SD实验组），以接受肝移植的正常SD大鼠为对照（SD对照组）；同种移植者的供者为Lewis大鼠，受者为BN大鼠（BN实验组），以接受肝移植的正常BN大鼠为对照（BN对照组）。术后观察受者的存活情况以及移植肝的组织学变化。结果肝硬化大鼠门静脉压力为（182．0±10．7）mm H2O，显著高于正常大鼠的（70．8±5．5）mm H2O（P〈0．01），移植后7d降至（82．7±10．7）mm H2O。同种移植组术后5～12d，移植肝组织中均可见中、重度急性排斥反应病理改变。同系移植者存活时间中位数均〉100d；同种移植者中，BN对照组和BN实验组受者肝移植后存活时间中位数均为10d。结论以Lewis大鼠为供者、肝硬化BN大鼠为受者制备的肝移植模型术后排斥反应的发生率较高，可作为肝移植后排斥反应相关研究的平台。

Objective To establish a model of orthotopic liver transplantation （OLT） in the rats with cirrhosis and observe the occurrence of postoperative rejection. Methods The cirrhosis model was established in SD or BN rats by subcutaneous injection of 500% carbon tetrachloride （CC14）. OLTs were performed in normal or cirrhosis rats （isotranplantation in SD→SD rats and homotransplantation in Lewis→BN rats） based on modified two-cuff technique. Histopathological changes and the post-operative survival time of the liver grafts were observed. Results The portal venous pressure （PVP） in cirrhosis rats was significantly higher than in normal rats （182. 0 ± 10. 7 mm H2O vs. 70. 8 ± 5.5 mm H20,P〈0. 01） ,and decreased on the 7th day after OLT （82.7 ± 10. 7 mm H2O）. The moderate or severe rejection of allografts was detected within 5-12 days after OLT in homotransplantation rats. The post-OLTs median survival time （MST） was more than 100 days in isotranplantation SD rats and 10 days in homotransplantation BN rats, respectatively. Conelusion In the liver transplantation model with Lewis rats as donors and BN rats as recipients, the incidence of postoperative rejection is high. The model can be effectively used to study allograft rejection or immune tolerance.