小鼠原位脂肪肝移植模型的建立

目的　建立了ob/ob小鼠脂肪肝移植模型 ,探讨保证建模成功的关键因素。方法　采用小鼠非动脉化肝移植技术 ,5～ 7周肥胖小鼠为供体 ,正常小鼠为受体 ,双袖套法行原位肝移植。受体肝组织行HE染色和油红O染色 ,血清ALT、AST水平检测采用常规生化分析法。结果非脂肪肝移植组 (lean to lean)受体长期存活率 (n =10 )为 70 % ,脂肪肝移植组 (ob/obtoagematchedlean)受体存活率为 0 (n =10 ) ,差异有显著性 (P <0 .0 5 )。脂肪肝移植给体积相当的正常小鼠 ,其短期存活率为 3 0 % (n =10 ) ,所有小鼠术后存活并苏醒 ,但均未超过 2 4h。脂肪肝移植受体ALT水平为 (62 85± 2 93 7)U /L ,AST为 (5 812± 2 942 )U /L ;而正常小鼠移植组ALT与AST水平分别为 (5 96± 114 )U /L ,(1796± 870 )U/L ,差异有显著性 (P <0 .0 5 ) ,组织学检测显示大量胆管中央凝固性坏死伴出血。结论　该模型的成功建立为我们提供了一种新的肝原发性肝无功能移植模型 ,为脂肪肝移植后脂肪肝细胞受损的机制研究奠定了基础。

Establishment of steatotic liver transplantation in the mouse

Objective To establish the model of ob/ob mouse orthotopic liver transplantion (OLT) and investigate the experience.Methods The techniques of a non-arterialized murine transplant model were applied.C57BL6 ob/ob mice aged 5-7 weeks (25-35) g and lean controls served as liver donors and recipients respectively.OLT was performed using a two-cuff technique at the infrahepatic cava and portal vein.The suprahepatic cava was anastomosed end to end and the bile duct was stented.The hepatic artery was not reconstructed.Results Lean-to-lean OLT was performed with 70% (n= 10) long-term survival.ob/ob-to-age-matched lean recipients had 0% (n= 10) survival due to size discrepancy.ob/ob livers were transplanted to size-matched lean recipients (>3 months old) with short-term survival of 30% (n= 10).These mice survived the operation,awakened,but expired within 24 h.Serum transaminases revealed a significantly higher injury profile in the recipients of the steatotic livers,and histology showed massive centrilobular coagulative necrosis with hemorrhage,the overall picture being that of primary nonfunction.Conclusion This novel use of ob/ob mouse for OLT provides us with a model for steatotic transplantation with PNF as the endpoint,and may help better understand the response of the steatotic liver to the insult of transplantation.