异种肝细胞移植防治大鼠急性肝功能衰竭的初步探讨

Therapeutic and prophylactic effects of xenogeneic hepatocyte transplantation in rat acute liver failure

目的 探讨异种肝细胞移植对大鼠急性肝功能衰竭的防治效果及其免疫排斥反应。方法 建立大鼠 90 %肝切除肝功能衰竭模型。切肝术前 1d分别植入豚鼠肝细胞和大鼠肝细胞 ,建立异种移植组、同种移植组及未移植对照组。观察受试大鼠的存活时间及切肝术后 2 4h血液生化指标改变 ,观察植入肝细胞被排斥的情况及受体总补体活性 (CH5 0 )、异种抗体IgG、IgM水平变化。 结果 ①未移植对照组中位存活时间为 2 1h ,同种移植组为 5 6h ,异种移植组为 4 0h。同种移植组及异种移植组存活时间均较未移植对照组延长 (P <0 .0 1和 0 .0 5 )。②异种移植组血糖和凝血酶原时间 (PT)改善较明显 (P <0 .0 5 ) ,同种移植组丙氨酸转氨酶、总胆红素、血糖、PT均有明显改善 (P <0 .0 5或 0 .0 1)。③受体CH5 0和异种抗体IgM水平下降与植入异种肝细胞排斥过程同步。结论 异种肝细胞移植对大鼠急性肝功能衰竭有防治作用 。

Objective To appraise the therapeutic and prophylactic effects of xenogeneic hepatocyte transplantation on rat acute liver failure and hepato cytes rejection. Methods 90% subtotal hepatectomy was done to establish rat acute liver failure model. The hepatocytes of guinea pig or rat were transplanted into the recipient one day before creating the xenogeneic group and allogeneic group. The control group was composed of non-transplant rats. The survival period and liver failure of rats were recorded. 24 hours after hepatectomy together with rejection of transplanted cells levels of CH50, xeno-specific antibody IgG and IgM in the recipients. Results ① The median survival periods was were 21 hours in the control group, 56 hours in the allogeneic group and 40 hours in the xenogeneic group. The survival periods of allogeneic group and xenogeneic group were longer than that of the control group (P<0.01 and P< 0.05 respectively). ②Blood glucose and prothrombin time improved obviously in xenogeneic group (P<0.05), while alanine aminotransferase, total bilirubin, blood glucose and prothrombin time were all significantly improved in the allogeneic group (P<0.05 or 0.01). ③Levels of CH50, xeno-specific antibody IgM in the recipients decreased synchrononsly with rejection.Conclusion Xenogeneic hepatocyte transplantation is effective in the prophylaxis and treatment of rat acute liver failure. Complement and xeno-specific antibody IgM are closely correlated with the hepatocytes rejection. (Shanghai Med J, 2004,27∶828-831)