低氧预适应对自体原位移植肝肝内胆管上皮细胞的影响

Effect of hypoxia preconditioning on intrahepatic cholangiocytes of autografted liver

目的探讨低氧预适应(HP)对自体原位移植肝肝内胆管上皮细胞的影响及其机制。方法大鼠随机分为3组:A组为自体肝移植组;B组为低氧预适应后行自体肝移植组;C组为假手术组。于术后24 h 3组检测血清总胆红素(TBIL),直接胆红素(DBIL),碱性磷酸酶(ALP);免疫组织化学法检测胆管上皮细胞VEGF的表达及其核增殖指数(PI);光镜下观察胆管上皮细胞的病理变化。结果 (1)血清TBIL,DBIL和ALP检测,与C组比较,A,B组都有不同程度的升高,但A组升高更明显。(2)各组胆管上皮细胞均有VEGF表达,其中B组表达最强;与C组比较,A,B组的胆管上皮细胞都有不同程度的增生,但B组的胆管上皮细胞PI升高更明显。(3)组织学检测显示,与B组相比,A组胆管上皮细胞损伤严重,细胞排列缺失明显,炎性细胞浸润增加。结论低氧预适应对移植肝肝内胆管上皮细胞具有保护作用,其机制可能与HP能诱导移植肝肝内胆管上皮细胞过度表达VEGF有关。

Objective To investigate the effect of hypoxia preconditioning（HP） on intrahepatic cholangiocytes of autogenic liver graft and its mechanism.Methods The models of autogenic liver transplantation were constructed,including group A（autogenic liver transplantation）,group B（hypoxic preconditioning before transplantation）,and group C（sham operation）.Blood samples were collected 24 huors after operation for examination of the serum total bilirubin（TBIL）,direct bilirubin（DBIL）and alkaline phosphatase（ALP）.Immunohistochemical method was used to detect the expression of vascular endothelial growth factor（VEGF）and proliferation rate of cholangiocytes.The pathological changes were observed by light microscope.Results（1）Compared with group C,the TBIL,DBIL,ALP was increased in group A and B,but increased more obviously in group A.（2）VEGF was detected in all groups,but in group B the expression was most obvious.As compared with group C,proliferation rate of cholangiocytes was higher in group A and B,but the proliferating cell nuclear antigen index（PI） was the highest in group B.（3） Compared with group B,the damage,inflammatory cell infiltrate and the absence of the cell arrange were more severe in group A.Conclusions HP has protective effect on cholangiocytes of autogenic liver graft,and its mechanism may relate with the over expression of VEGF on cholangiocytes induced by HP.