ＨＯ-１持续高表达对ＤＡ到Ｌｅｗｉｓ大鼠肝移植急性排斥反应的影响

目的:探讨血红素氧化酶-1(hemeoxygenage-1,HO-1)在DA到Lewis大鼠肝移植中对急性排斥反应的影响及其机制.方法:建立DA到Lewis大鼠肝移植急性排斥模型,实验分3组,各12对.A组供体术前24 h阴茎背静脉注射5ml/kg生理盐水作为对照;B组供体术前24 h阴茎背经脉注射HO-1诱导剂钴原卟啉(CoPP),C组供体给予HO-1抑制剂锌原卟啉(ZnPP),移植后持续予相同处理直至受体死亡.术后7天,各组处死6只,取外周血及肝脏标本,测定血清ALT,DBIL水平,组织病理观察排斥反应程度,RT-PCR及Western blot法测定移植物内HO-1 mRNA,Foxp3 mRNA及其蛋白表达情况,余观察生存期.结果:术后7天,B组血ALT,TBIL水平与A组,c组相比,差异有统计学意义(P＜0.01);病理示B组移植肝排斥反应程度轻于A,C组;B组HO-1和Foxp3 mRNA及其蛋白的表达均强于A,C组;B组受体存活时间(29.83±1.40)天较A组(13.00±0.52)天与C组(11.67±0.42)天显著延长(P＜0.01),而A,C组之间差异无统计学意义(P＞0.05).结论:诱导移植肝HO-1持续高表达,可通过促进移植物内Foxp3表达增强,发挥免疫抑制作用,减轻移植肝急性排斥反应.

Effect of continuous expression of hemeoxygenase-1 on acute allograft rejection:liver transplantation experiment from DA to Lewis rat

Objective:To investigate the effects and mechanism of hemeoxygenase-1(HO-1) on acute liver transplantation rejection model. Methods:36 male DA rats used as donors were randomly divided into 3 groups:Group A was injected via vena dorsalis penis with 0.9%NaCl(5 ml/kg);Group B was injected via vena dorsalis penis with cobalt-protoporphyrin(CoPP) 5 ml/kg,hemeoxygenase-1 inducer;and Group C was injected via vena dorsalis penis with zinc-protoporphyrin(ZnPP) (5 ml/kg),hemeoxygenase-1 inhibitor,before livers were harvested. After transplantation,recipients were given the above treatments daily. Six recipients in each group underwent collection of blood and liver tissues 7 days after transplantation to detect the changes of serum enzymesalanine aminotransferase(ALT),total bilirubin(TBIL)] and the grafts histology. The mRNA and protein expressions of HO-1 and Foxp3 in the transplanted livers were detected by RT-PCR. The other 6 recipients in each group were used to observe the survival time. Results:The survival time of Group B(29.83 ± 1.40)d] was significantly longer than that of Group A(13.00 ± 0.52)d,P < 0.01] and Group C(11.67 ± 0.42)d,P < 0.01]. The values of ALT and TBIL of Group B were significantly lower than those of Group A and C(all P < 0.01). The histological manifestation of the grafts rejection in group A and C were more severe than group B. The expressions of HO-1 mRNA,Foxp3 mRNA in the transplanted livers of Group B were significantly higher than those of Group A. Both mRNA and protein expressions of HO-1 and Foxp3 of Group C were not significantly different from those of Group A. Conclusion:Continuous expression of HO-1 alleviated the reaction of acute rejection in liver transplantation. This effect partly depends on HO-1-mediated Foxp3 activation.