辅助性部分原位肝移植治疗小鼠急性肝功能衰竭  

The therapy of auxiliary partial orthotopic liver transplantation for acute liver failure in mice

作　　者：高丹[1] 龙新 朱鹏 程琪 Gao dan;Long Xin;Zhu Peng;Cheng Qi(Maternal and Children Hospital of Hubei Province,Wuhan 430070,China)

机构地区：[1]华中科技大学附属湖北妇幼保健院甲乳外科,武汉430070 [2]华中科技大学同济医学院附属同济医院肝脏外科中心,武汉430030

出　　处：《中华器官移植杂志》2018年第12期745-749,共5页Chinese Journal of Organ Transplantation

基　　金：国家自然科学青年基金(81700571);华中科技大学附属湖北妇幼保健院院内基金(220936001).

摘　　要：目的利用小鼠急性肝功能衰竭模型和辅助性部分原位肝移植模型,初步研究辅助性部分原位肝移植治疗急性肝功能衰竭的作用机制。方法小鼠急性肝衰竭模型作为受体,小鼠左外叶肝作为移植供肝,门静脉吻合采用袖套法,供肝流出道静脉与受体的肝上下腔静脉行端侧吻合,胆总管使用空心管套入小肠实现胆肠吻合。观察两组小鼠术后7 d存活率、转氨酶指标、自身肝细胞凋亡指数、供肝和自身肝细胞再生等情况。结果急性肝功能衰竭组小鼠术后48 h的总体存活率为13.6%(3/22),辅助性部分肝移植组的术后48 h存活率为81.8%(27/33),两者存活率存在明显差异。在术后的样本检测对比中,与急性肝功能衰竭组相比,肝移植组小鼠的血清谷丙转氨酶、总胆红素、血氨浓度明显降低,自身肝细胞的凋亡比例有明显减少。肝移植组的自身肝比对照组的自身肝HE染色显示其肝细胞坏死和肝小叶结构紊乱程度明显减轻,且移植组的自身肝在供肝的支持下,发生了明显的肝细胞分裂和再生。结论辅助性部分原位肝移植作为治疗急性肝功能衰竭的一种有效手段,其机制是在一定体积的辅助肝脏的支持下,通过减少自身肝细胞的凋亡、促进自身肝再生,恢复肝脏功能等途径来提高存活率,同时供肝在移植后会迅速再生,也对肝功能的恢复起到重要作用。Objective Auxiliary partial orthotopic liver transplantation (APOLT) is an effective treatment for fulminant liver failure. However, information on the experimental problem and hepatocyte proliferation mechanism of native and donor liver is lacking. In this study, an effective APOLT model for acute liver failure (ALF) in mice is established to address these issues. MethodsWe created an ALF mouse model wherein about 82% of liver tissue was resected with total hepatic vascular exclusion. The procedure lasted 25 min. Donor liver was transplanted to the left lateral lobe of the C57BL of the recipient. ResultsIn the ALF group, most mice died within 2-day because of liver failure. Of the 33 mice that received APOLT, 27 lived for more than 7-day. Significantly increased the levels of transaminases, serum ammonia, total bilirubin and liver cell apoptosis were observed in the ALF group, whereas treatment with APOLT reduced all these parameters. In addition, significant regeneration of the native liver with the auxiliary liver graft was observed in the APOLT group. ConclusionIt was proved that APOLT could totally meliorate the liver functions, reduce the native liver apoptosis, and facilitate the native liver proliferation in acute liver failure by means of mouse APOLT model.

关 键 词：肝移植 小鼠 急性肝功能衰竭 模型 凋亡 肝再生 

分 类 号：R657.3[医药卫生—外科学]