异种肝细胞移植防治大鼠急性肝功能衰竭

The therapeutic effect of xenogeneic hepatocyte transplantation on rats with 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治疗效果。方法 :切除大鼠 90 %肝脏 ,建立急性肝功能衰竭模型。分离异种豚鼠和同种异体Sprague Dawley鼠肝细胞 ,切肝术前 1天植入受体脾脏内。观察受试大鼠存活时间、切肝术后 2 4小时血生化改变和脾脏切片表现。结果 :①中位存活时间 ,对照组为 2 1小时 ,同种组为 5 6小时 ,异种组为 40小时。同种组存活时间较对照组长 (P <0 .0 1) ,异种组亦延长 (P <0 .0 5 )。②移植组部分血生化指标有所改善。异种组中仅血糖和凝血酶原时间改善较明显 (P <0 .0 5 ) ,同种组中谷丙转氨酶、总胆红素、血糖和凝血酶原时间都有明显改善 (P <0 .0 5或P <0 .0 1)。③肝细胞植入后 48小时 ,异种组脾脏内仅存少量萎缩的肝细胞 ,同种组脾脏内仍散在健存肝细胞。结论 :异种肝细胞移植对大鼠急性肝功能衰竭有防治作用 ;要提高移植效果 。

Objective:To investigate the therapeutic effect of xenogeneic hepatocyte transplantation on rats with acute liver failure.Methods:90% of the rat liver was resected to establish acute liver failure model. Hepatocytes of xenogeneic guinea pig and allogeneic Sprague Dawley rat were isolated and transplanted into the spleen of the recipient 1 day before hepatectomy. Survival time was observed. Biochemical changes in blood and spleen sections were studied 24 hours after hepatectomy.Results:①Median survival time was 21 hours in control group, 56 hours in allogeneic group and 40 hours in xenogeneic group. Survival time of allogeneic group and xenogeneic group were longer than control group (P<0.01 and P<0.05 respectively). ②Some of biochemical changes in transplantation groups were better. Only blood glucose and prothrombin time were improved obviously in xenogeneic group (P<0.05), while alanine aminotransferase, total bilirubin, blood glucose and prothrombin time were all significantly improved in allogeneic group (P<0.05 or P<0.01). ③Only a few shrinked hepatocytes could be found in spleens of xenogeneic group 48 hours after hepatocyte transplantation, but in allogeneic group there were some alive.Conclusion:Xenogeneic hepatocyte transplantation is effective in the treatment of rats with acute liver failure. Early stage immune rejection should firstly be resolved to improve the effect of xenotransplantation.