肝硬化大鼠模型肝细胞移植途径的筛选

目的 通过比较4种同种异体肝细胞移植方法治疗肝硬化大鼠模型的疗效,筛选出较好的细胞移植途径.方法 50只经证实成模的肝硬化大鼠模型动物被完全随机分为5组:肝动脉移植组(G1)、门静脉移植组(G2)、脾动脉移植组(G3)、尾静脉移植组(G4)及对照组(G5).前4组分别自肝动脉、门静脉、脾动脉及尾静脉注射肝细胞悬液2 ml(细胞数量为2×106),对照组(G5)不作干预.移植前后对各组大鼠行肝功能检测及术后处死大鼠取肝脏作病理评分.结果 G1、G2组移植后前3周血清白蛋白水平逐渐下降,第5周后逐渐回升,到第7周达到峰值(15.4±2.3)g/L,(15.4±2.1)g/L].G1、G2组移植后前3周血清总胆红素水平逐渐上升,到第5周后逐渐回落,到第7周达到移植前的水平(13.62±2.32)μmol/L].G5组移植前后血清总胆红素水平变化不明显;术后病理G3组改善最为明显,G1、G2组次之,G4组再次之,G5改善情况最差.结论 在针对肝硬化大鼠模型不同的移植途径中,经脾动脉途径移植肝细胞,术后病死率较低,能更有效地改善肝脏功能及减轻肝细胞的变性和坏死.

Selection on delivery route of cell transplantation for treatment of hepatic cirrhosis in rat models

Objective To compare the efficacy of allogeneic hepatocyte transplantation in rat models of hepatic cirrhosis and to select the optimal route from four different approaches.Methods Fifty rats confirmed to have hepatic cirrhosis were randomly divided into 5 groups:the intra-hepatic artery group (Group 1) , portal vein group (Group 2),splenic artery(Group 3),tail vein group (Group 4) and the control group (Group 5).The first 4 groups received injection of 2 ml hepatocyte suspension (cell number 2 x 106) through corresponding vessels respectively, while the control group remained untreated. Liver function such as albumin (Alb) and total bilirubin (TBil) was measured in each group of rats before and after transplantation. Pathology of the liver tissue was studied in each group at 8 weeks after translplantation. Results In Groups 1 and 2, the level of Alb became lower during the first 3 weeks after transplantation, gradually recovered by week 5, and then peaked at week 7 (15.4±2.3)g/L, (15.4±2.1)g/L]; the level of TBil increased during the first 3 weeks, declined by weeks 5, and returned to baseline by week 7 (13.62± 2.32)μmol/L]. The serum level of total bilirubin appeared comparable before and after transplantation. Best improvement in liver pathology was found in Group 3, followed by Groups 1 or 2, Group 4, and the worst in Group 5. Conclusions Among different routes of hepatocyte transplantation in rat models of hepatic cirrhosis, the splenic artery route results in the lowest mortality, and can be more effective in improving liver functions and reducing the liver cell degeneration and necrosis.