供受者肝重量比对大鼠部分肝移植后排斥反应的影响

Influence of graft weight to recipient liver weight on allogenic rejection after partial liver transplantation

目的探讨不同的供受者肝重量比（GW/RLW）对于大鼠部分肝移植术后排斥反应的影响。方法以BN大鼠为供鼠，Lewis大鼠为受鼠，分别行全肝移植（A组）、GW/RLW〉33%部分肝移植（B组）和GW/RLW〈30%部分肝移植（C组）。术后观察28 d，通过比较术后各组存活时间、黄疸、体重曲线和移植肝脏Banff RAI评分来评估急性排斥反应。再另设GW/RLW〉33%部分肝移植（B1组）和GW/RLW〈30%部分肝移植（C1组），在术后48 h和第7天比较移植物中的白细胞介素2（IL-2）、颗粒酶B、穿孔素和CD3的mRNA水平。并在术后第7天，比较B1组和C1组中的肝功能、总胆红素、B7-H1的mRNA水平和Ki67阳性肝细胞数。结果A、B两组受鼠术后28 d内全部存活，C组受鼠在术后22 d内全部死亡。B、C组受鼠黄疸出现时间早于A组（P〈0.01），体重增长曲线低于A组（P〈0.05）。C组的体重增长曲线则低于B组（P〈0.05）。A组移植肝可见少量淋巴细胞浸润，未见血管内皮增厚；B组移植肝可见汇管区存在淋巴细胞的浸润，中央静脉内皮明显增厚；C组移植肝内可见大量淋巴细胞浸润，血管内皮明显增厚，正常的肝细胞排列形态被破坏，其Banff RAI评分高于A组和B组。移植术后第7天，C1组肝移植物中的穿孔素、颗粒酶B、IL-2和CD3 mRNA水平，以及肝酶和移植肝增重均高于B1组，差异有统计学意义（P〈0.05）。且C1组的免疫抑制共刺激分子B7-H1的mRNA水平低于B1组（P〈0.05）。但两组间的Ki67阳性的肝细胞数比值的差异没有统计学意义。结论GW/RLW降低时，大鼠部分肝移植术后的免疫排斥反应被增强。

Objective To investigate the severity of allogenic rejection after partial liver transplantation （PLTx） with different graft weight to recipient liver weight （GW/RLW）.MethodsThe full-size liver transplantation （group A）, GW/RLW 〉33% PLTx （group B） and GW/RLW 〈30% PLTx （group C） were set up using BN rats and Lewis rats as donors and recipients, respectively. All recipients were observed for 28 days. The Banff RAI grading, survival rate, jaundice and body weight recovery were evaluated to determine the severity of acute allogeneic rejection. Two PLTx groups, group B1 （GW/RLW〉33%） and group C1 （GW/RLW〈30%）, were established to assess the mRNA level of IL-2, GranzymeB, Perforin and CD3 48 h and 7 days postoperatively. Additionally, the mRNA level of B7-H1, the ratio of Ki67＋ hepatocytes and the liver enzymes were also assessed 7 days postoperatively.ResultsAll recipients in group C died within 22 days postoperatively, presenting with severe lymphocytic infiltration and vascular endothelialitis. All recipients in group A and group B survived until the end of observation time. All recipients in group A survived and presented with a mild lymphocytic infiltration and rare vascular endothelialitis. Group B presented with moderate lymphocytic infiltration and moderate vascular endothelialitis. The Banff RAI grading in group C was significantly higher than that in group A and group B （P〈0.05）. In accordance with the result of histology and survival rate, group B and group C presented with earlier jaundice and lower body weight recovery than that of group A （P〈0.05）. As compared with group B1, group C1 presented with higher mRNA levels of Perforin, GranzymeB, IL-2 and CD3, higher level of liver enzymes and heavier liver graft weights. Besides, the mRNA level of immunosuppresive molecule B7-H1 in group C1 was lower than that of group B1. However, there was no significant difference in the ratio of Ki67＋ hepatocytes between group B1 and group C1.ConclusionThe allogenic liver rejection may be enhanced by reducing the GW/RLW.