小剂量环孢素A和骨化三醇联用预防大鼠原位肝移植后急性排斥反应的效果

Preventing allografts from acute rejection following orthotopic liver transplantation with low dose of CsA and 1,25-dihydroxyvitamin D_3

目的 探讨小剂量环孢素A(CsA)和骨化三醇 [1,2 5 (OH) 2 D3 ]对预防原位肝移植后急性排斥反应的协同效应。方法 以SD大鼠和Wistar大鼠分别作为供者和受者 ,采用Kamada方法建立大鼠原位肝移植模型。受者随机分成Ⅰ、Ⅱ、Ⅲ、Ⅳ组。Ⅰ组为对照组 ;Ⅱ组和Ⅲ组移植后分别接受全剂量CsA和全剂量骨化三醇治疗 ;Ⅳ组移植后接受小剂量CsA和骨化三醇联合治疗。观察移植后生存期及移植后 5、7、12d肝组织病理学变化和IFN γmRNA表达水平等指标。结果 Ⅳ组 5 / 6受者长期存活 ,生存期较Ⅰ组显著延长 (P <0 .0 5 ) ;与Ⅱ组或Ⅲ组比较 ,差异均无显著性 (P >0 .0 5 )。Ⅳ组移植后各时点排斥反应平均病理学分级分别为 0 .6 7,1和 0 .6 7级 ,较Ⅰ组减低 ,差异有显著性 (P <0 .0 5 ) ;与Ⅱ组或Ⅲ组比较 ,差异均无显著性 (P >0 .0 5 )。Ⅳ组肝组织IFN γmRNA表达处于低水平 ,较Ⅰ组明显受抑制 (P <0 .0 5 ) ;与Ⅱ组比较 ,差异无显著性 (P >0 .0 5 ) ;与Ⅲ组比较 ,除移植后 7d外 ,差异均无显著性 (P >0 .0 5 )。结论 原位肝移植后小剂量环孢素A和骨化三醇联用 ,可以有效预防急性排斥反应 ,延长受者生存期。两者具有明显的正协同作用。

Objective To investigate the synergistic effect of low dose of CsA and 1,25-dihydroxyvitamin D 3 in the treatment of acute rejection following orthotopic liver transplantation.Methods Orthotopic rat liver transplantation model performed according to Kamada's technique was employed. SD and Wistar rats served as donors and recipients respectively. Recipients were divided randomly into 4 groups. GroupⅠ: Control; Groups Ⅱ and Ⅲwere treated with full dose of CsA and 1,25-dihydroxyvitamin D 3 respectively; Group Ⅳ was subjected to administration of low dose of CsA combinated with 1,25-dihydroxyvitamin D 3. Survival posttransplantation as well as pathological rejection grade and IFN-γmRNA expression on the day 5, 7, 12 after transplantation was observed. Results In group Ⅳ,the survival in 5/6 recipients were significantly increased in comparison with Group Ⅰ ( P < 0.05 ), but not significantly different from that in group Ⅱ or group Ⅲ ( P > 0.05 ) . The average pathologic rejection grade in group Ⅳ was 0.67 , 1 and 0.67 at the 5?th, 7?th, 12?th day posttransplantation respectively, markedly lower than in group Ⅰ ( P < 0.05 ). IFN-γ mRNA expression in the liver tissues in group Ⅳ was at a low level on each time point. IFN-γ mRNA expression was not significantly different ( P > 0.05 ) from either groupⅡ or group Ⅲ except on the day 7 posttransplantation.Conclusion Administration of low dose of CsA combined with 1,25-dihydroxyvitamin D 3 is synergistic in preventing allografts from acute rejection and prolonging survival of recipients after orthotopic liver transplantation.