CAJ | 학술논문

目的建立大鼠原位肝脏移植急性排斥与自然耐受模型.方法采用近交系雄性DA大鼠与Lewis大鼠互为供受体,改良"二袖套"法建立大鼠原位肝脏移植(rat orthotopic liver trans-plantation,ROLT)模型84例.实验分为4组:排斥组(DA→Lewis,n=12),FK506处理排斥组[DA→Lewis,n=24,术后1～7 d用FK506 0.2 mg/(kg·d)灌胃],耐受组(Lewis→DA,n=24),同基因组(DA→DA,n=24).各组中随机取6例观察生存期,其余分别于术后7、14、28 d处死6例,收集外周血及肝脏标本.检测血清标本天冬氨酸转氨酶(aspartate aminotransferase,AST)、总胆红素(total bilirubin,TBIL)浓度,病理学检查移植物排斥反应程度.结果排斥组中位生存时间(median surviv-al time,MST)为12 d,而FK506处理排斥组MST为76 d,较排斥组明显延长(vs排斥组,P<0.01).耐受组与同基因组的MST均>120 d.术后7 d,排斥组血清AST、BILI浓度均明显高于其余3组(P<0.05);术后14 d,FK506处理组、耐受组和同基因组血清AST、TBIL浓度无明显差异.术后28 d,FK506处理组血清AST、TBIL浓度较耐受组和同基因组明显升高(P<O.05).肝脏病理表现:术后7 d,排斥组为严重的急性排斥反应,Banff评分Ⅲ级;耐受组为I～Ⅱ级,同基因组与FK506处理排斥组为O～I级.术后28 d,FK506处理排斥组为慢性排斥反应表现,耐受组和同基因组移植无明显排斥反应表现.结论 DA与Lewis大鼠品系组合,可以建立稳定可靠的肝脏急性排斥模型与自然耐受模型,两种模型的生存期、肝功能变化、移植物病理表现,符合急性排斥和自然耐受的特点,是进行肝移植免疫研究的良好的动物模式.
목적 건립대서원위간장이식급성배척여자연내수모형.방법 채용근교계웅성DA대서여Lewis대서호위공수체,개량"이수투"법건립대서원위간장이식(rat orthotopic liver trans-plantation,ROLT)모형84례.실험분위4조:배척조(DA→Lewis,n=12),FK506처리배척조[DA→Lewis,n=24,술후1～7 d용FK506 0.2 mg/(kg·d)관위],내수조(Lewis→DA,n=24),동기인조(DA→DA,n=24).각조중수궤취6례관찰생존기,기여분별우술후7、14、28 d처사6례,수집외주혈급간장표본.검측혈청표본천동안산전안매(aspartate aminotransferase,AST)、총담홍소(total bilirubin,TBIL)농도,병이학검사이식물배척반응정도.결과 배척조중위생존시간(median surviv-al time,MST)위12 d,이FK506처리배척조MST위76 d,교배척조명현연장(vs배척조,P<0.01).내수조여동기인조적MST균>120 d.술후7 d,배척조혈청AST、BILI농도균명현고우기여3조(P<0.05);술후14 d,FK506처리조、내수조화동기인조혈청AST、TBIL농도무명현차이.술후28 d,FK506처리조혈청AST、TBIL농도교내수조화동기인조명현승고(P<O.05).간장병리표현:술후7 d,배척조위엄중적급성배척반응,Banff평분Ⅲ급;내수조위I～Ⅱ급,동기인조여FK506처리배척조위O～I급.술후28 d,FK506처리배척조위만성배척반응표현,내수조화동기인조이식무명현배척반응표현.결론 DA여Lewis대서품계조합,가이건립은정가고적간장급성배척모형여자연내수모형,량충모형적생존기、간공능변화、이식물병리표현,부합급성배척화자연내수적특점,시진행간이식면역연구적량호적동물모식.
Objective To establish rejection and tolerance model of rat orthotopic liver transplantation(ROLT).Methods Eighty-four cases of ROLT with inbred male DA and Lewis rats serving as donors and recipients respectively, undergoing modified Kamada two-cuff technique were divided into 4 groups: rejection group(DA→Lewis,n=12),rejection group treated with FK506(DA→group(Lewis→DA,n=24),isogenic group(DA→DA,n=24).After transplantation,6 recipients sacrificed one day 7,14 and 28,respectively.The serum AST and bilirubin levels and graft histological changes were evaluated. Results The median survival time(MST)of rejection group was shorter than FK506 treatment group(1 2 d vs 76 d,P<0.01)and the MST in tolerance and isogenic group was more than 120 d. In 7 d after transplantation, the serum concentrations of AST and TBIL in reiecrion group were significantly higher than those in the other three groups(P<O.05).0n the 14 th day, there was no statistical difference between the three groups excluding rejection group, but when it came to the 28 th day, the serum AST and TBIL levels in tolerance and isogenic group were evidentiy lower than those in FK506 treatment group(P<0.05).The graft Banff scale on the 7 th d post-transplantation in rejection group was higher than that in other three groups (rejection group,Ⅲ;tol-eranee group,I-Ⅱ;isogenic group and FK506 treatment group,O-Ⅰ).on the 28 th day,the grafts in FK506 treatment group manifested chronic rejection but not in tolerance and isogenie group.Conclusion DA and Lewis rat strain combination can be applied to establish a stable and reliable model of rat liver transplantation,.of Which the liver function changes, graft histological manifestations, and survival time are consistent with the features o acute rejection and natural tolerance. This model can be an ideal choice for the immunologecal study of live transplantation.