两种大鼠原位肝移植急性排斥模型的对比观察

Comparative Analysis on Two Models of Rat Orthotopic Liver Transplantation for Acute Rejection

目的对比观察两种大鼠原位肝移植急性排斥模型。方法进行改良二袖套法大鼠原位肝移植;分为Sprague Dawley(SD)→SD组(24例),SD→Wistar组(24例)及Dark Agouti(DA)→Lewis组(24例)。术后3,5,7,10d分别随机处死4只受鼠,检测血清丙氨酸转氨酶(ALT)和总胆红素(TBIL)变化,并观察肝脏病理组织学改变;每组剩余受鼠进行生存分析。结果手术成功率为94.4%;DA→Lewis组中位生存时间(8d)短于SD→Wistar组(16d)(P=0.000)。SD→Wistar组71.4%受鼠移植肝急性排斥反应逐渐加重(RAI:3～7分),28.6%逐渐好转;DA→Lewis组受鼠移植肝发生重度急性排斥反应(RAI:7～9分)。在7,10d,DA→Lewis组受鼠血清ALT、TBIL浓度均高于SD→Wistar组(7d:P=0.000、0.007;10d:P均=0.000)。结论 SD→Wistar组合的大鼠肝移植术后大部分可发生急性排斥反应,但会出现自发耐受现像,从而导致急性排斥反应基础研究偏移;而DA→Lewis组合的大鼠肝移植术后均出现重度的急性排斥反应,是一种理想的急性排斥反应模型。

Objective To compare two rat orthotopic liver transplantation model for acute rejection. Method Rat orthotopic liver transplantation was carried out with improved two-cuff method. Transplantation setting. Three goups of rat, 24 rats for each as following setting： SpragueDawley （SD）→ SD, SD→Wistarand Dark Agouti （DA）→Lewis. At date 3, 5, 7 and 10, four recipient rats were randomly selected and sacrificed, blood serum and liver tissue were collected for ELISA detection of serum alanine aminotransferase （ALT） and total bilirubin （TBIL）, and for pathological analysis, the rest 8 recipient rats in each group were left for survivial analysis. Results 68 out of total 72 rats survived operation, operation success ratio was 94.4%. The median survival day of recipient rats in DA→Lewis group was 8 days, which was shorter than thatof SD→Wistar group （16 d） （P=0. 000）, 71.4% recipient rats in SD→ Wistar group developed gradual severe （RAI： 3 points-7 points） liver grafts acute rejection, 28.6% recipient rats showed decreased liver grafts acute rejection. All recipient rats in DA→Lewis group developed severe （RAI： 7 points-9 points） liver grafts acute rejection, In 7,10 d, serum ALT, TBIL concentrations of DA→Lewis group were higher than those in SD→Wistar group （7 d： P=0. 000, 0. 007; 10 d： P=0. 000, 0. 000）. Conclusion Most of rats liver in combination of SD→Wistar developed acute rejection after liver transplantation, there were spontaneous tolerance occurent, resulting in basic research shift of acute rejection. DA→Lewis rat liver transplantation was able to develop severe acute rejection, which was considered an ideal model for acute liver rejection.