不同品系大鼠之间肝移植排斥反应的比较研究

Comparison on liver transplantation rejection among various strains combination of rats

  • 摘要:
      目的   比较不同品系大鼠之间肝移植排斥反应特点。
      方法   依据大鼠不同品系分成对照组SD→SD(A组),实验组Wistar→SD(B组)、Lewis→BN(C组)以及DA→Lewis(D组)4个组,采用Kamada双袖套法建立大鼠原位肝移植模型。比较各组受体大鼠术后10 d血清肝功能指标丙氨酸转氨酶(ALT)、总胆红素(TB)和白蛋白(Alb)、血清白细胞介素(IL)-2和IL-10水平、急性排斥反应组织病理学分级和术后平均生存时间。
      结果   与A、B组比较,C组和D组的血清ALT和TB明显升高,Alb明显降低,差异均有统计学意义(均为P<0.05)。与C组比较,D组的TB明显升高,Alb明显降低,差异均有统计学意义(均为P<0.05)。与A组比较,B、C、D组大鼠血清IL-2和IL-10水平均明显升高,C组和D组的IL-2/IL-10亦明显升高,差异有统计学意义(均为P<0.05)。与B组比较,C组和D组大鼠血清IL-2水平明显升高,D组的IL-2/IL-10亦明显升高,差异有统计学意义(均为P<0.05)。与C组比较,D组大鼠血清IL-2水平明显升高,D组的IL-2/IL-10亦明显升高,差异有统计学意义(均为P<0.05)。肝组织病理学检查显示,A组大鼠肝组织未见明显排斥反应,排斥活动性指数(RAI)评分(1.8±0.7)分;B组RAI评分(3.1±1.3)分,属轻度或不明确性排斥反应;C组RAI评分(6.9±0.8)分,属中~重度排斥反应;D组RAI评分(8.8±0.5)分,属重度排斥反应。各组间RAI评分比较以及组间两两比较,差异均有统计学意义(均为P<0.05)。A组、B组、C组、D组受体大鼠术后平均生存时间分别为(119.3±1.9)d、(116.9±8.3)d、(53.4±6.1)d、(12.1±2.4)d,A组与B组的生存时间比较差异无统计学意义,余各组两两比较差异均有统计学意义(均为P<0.05)。
      结论   4种组合中,大鼠DA→Lewis模型排斥反应最剧烈,Lewis→BN次之,而Wistar→SD最轻,接近于免疫耐受。

     

    Abstract:
      Objective   To compare the rejection of liver transplantation in different strains combination of rats.
      Methods   Four transplantation models of various strain combinations were established including the control group SD (donor) to SD (recipient) (group A) and the experimental groups Wistar to SD(group B), Lewis to BN(group C) and DA to Lewis(group D). Orthotopic liver transplantation model of rats were constructed by Kamada's two cuff technique. And serum hepatic functions in 4 groups of recipient rats at 10th day after liver transplantation were compared, which was including alanine aminotransferase (ALT), total bilirubin (TB) and albumin (Alb). Meanwhile the serum levels of interleukin(IL)-2 and IL-10, rejection activity index(RAI) at 10th day after liver transplantation and the average survival time of recipient rats were investigated.
      Results   Compared with group A and B, the serum levels of ALT and TB of group C and D increased obviously, while Alb decreased significantly. Compared with group C, TB of group D increased obviously, while Alb decreased remarkably. All of the differences were statistically significant (all in P<0.05). Compared with group A, the serum levels of IL-2 and IL-10 in group B, C and D all elevated significantly, and IL-2/IL-10 in group C and D increased remarkably too (all in P<0.05). Compared with group B, IL-2 in group C and D increased significantly, and IL-2/IL-10 in group D also elevated significantly. Compared with group C, both IL-2 and IL-2/IL-10 in group D increased significantly. All the differences were statistically significant (all in P<0.05). Hepatic histopathological examination showed that obvious rejection did not occur in the recipient rats of group A, which rejection activity index (RAI) was scored 1.8±0.7. The RAI score of Group B,C and D were 3.1±1.3, 6.9±0.8 and 8.8±0.5, which belonged to mild or vague rejection, moderate to severe rejection and severe rejection respectively. All the RAI scores comparison among and between each group had statistical differences (all in P<0.05). The average survival time of recipient rats in group A, B, C and D were (119.3±1.9) d, (116.9±8.3) d, (53.4±6.1) d and (12.1±2.4) d respectively. There was no statistically significant difference between group A and B, while the comparison between any other group was statistically significant (all in P<0.05).
      Conclusion   In four different rats strains combination, the rejection is most serious in the model of DA (donor) to Lewis (recipient), moderate in Lewis to BN, mildest and near to tolerance in Wistar to SD.

     

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