近交系大鼠肝移植急性排斥模型的建立及排斥反应观察

Establishment of acute rejection model of orthotopic liver transplantation in inbred rats

目的建立近交系大鼠肝移植急性排斥模型并观察其排斥反应的规律。方法近交系大鼠随机分为G1(BN-BN)、G2(SD-Wistar)和G3(LEW-BN)3组,每组18对。采用改良"二袖套法"大鼠原位肝移植模型,观察一般情况,生存期,术后第3、7、14、21天血清丙氨酸氨基转移酶(ALT)、总胆红素(TBIL)及移植肝病理学变化,根据Banff标准判断排斥反应强度。结果G1、G2大鼠1月存活率为100%;G3大鼠急性排斥反应于术后第3天始发生,第7天后逐渐加重,第14天达到高峰,除并发症致死外,余大鼠均在20天内死于Ⅲ级排斥反应。G3术后各时相点ALT、TBIL均明显高于G1、G2(P<0.05)。G3移植肝病理检查呈典型的排斥反应,而G1、G2没有。结论LEW-BN大鼠组合为稳定的大鼠肝移植急性排斥模型;但近交系大鼠手术耐受性差,建模难度大,熟练的显微外科技术是模型成功的关键。

Objective To summerize the technique and method for orthotopic liver transplantation in inbred rats and the observed characteristics of acute rejection. Methods The experiment was proceeded in three groups ： Group 1 （ G1, from BN to BN）, Group 2 （G2, from SD to Wistar） and Group 3 （G3, from LEW to BN）. The rat orthotopie liver transplantation （ROLT） model was established by modified Kamada＇s two cuff technique. The serum levels of alanine aminotransferase （ALT） and total bilirubin （TBIL） were measured on the 3rd, 7th, 14th and 21st days after the transplantation. The pathological changes of the transplanted livers were finally observed. Results The rate of survival for 1 month was 100% in G1 and G2,while the recipients in G3 all died within 20 days after the operation, showing physical signs, abnormal liver functions and pathologies typical of class Ⅲ acute rejection. Besides, the pathological examination excluded the presence of rejection in G1 and G2. Conclusion LEW to BN combination could be an ideal choice to build ROLT model, stable and easy to standardize. But there may be technical difficulties due to its poor tolerance. The sophisticated mierosurgical teehniques are the key to achieve success.