摘要
目的探讨骨化三醇延长大鼠肝移植后受体生存期的机理。方法观察肝移植后受体大鼠应用骨化三醇前后锌指蛋白A20及其下游基因表达的变化。结果原位肝移植后预防性应用骨化三醇可以抑制急性排斥反应(RAI 3．0±1．0 vs 8．7±0．6,P＜0．05),保护移植物功能[AST：(334±40)U/L vs(2572±537)U/L,P＜0．01；BIL：(38±11)mmol/L vs(159±47)mmol/L,P＜0．01],延长移植后受体生存期[100 d的生存率(83．33±29．81)%vs(66．67±37．65)%,P＜0．01]。同时,预防性应用骨化三醇后移植物局部Th1类细胞因子浓度明显降低[IL-2浓度(80．61±18．63) ng/ml vs(770．99±92．92)ng/ml,P＜0．01；IFN-γ浓度(230．05±47．42)ng/ml vs(984．19±166．16) ng/ml,P＜0．01]。其上游调控因子NF-(?)B核内表达水平明显降低,抑制蛋白I_(?)B和锌指蛋白A20表达水平明显增强。结论原位肝移植后预防性应用骨化三醇可以诱导“细胞保护性”基因A20表达,从而抑制蛋白I_(?)B的降解,抑制NF-_(?)B活化,并阻断损伤性细胞因子的表达,抑制急性排斥反应,延长移植后受体生存期。
Objective To explore the mechanism by which calcitriol prolongs recipient survival following rat allogeneic liver transplantation. Methods We investigated the alterations in A20 expression and the down-stream genes after prophylactic treatment with calcitriol following liver transplantation. Results Calcitriol significantly inhibited acute rejection （RAI 3.0 ± 1.0 vs 8.7 ± 0. 6, P 〈 0. 05 ）, protected allograft function [AST： （ 334 ± 40 ） U/L vs （ 2572 ± 537 ） U/L, P 〈 0. 01 ; BIL： （ 38 ± 11 ） mmol/L vs （ 159 ±47） mmol/L, P 〈0.01 ] , and prolonged recipient survival [95% confidence interval of suvival on 100 d posttransplantation： （ 83.33 ± 29. 81 ） % vs（ 66. 67 ± 37.65 ） %, P 〈 0. 01 ]. Concentration of Th1-type cytokine in allograft decreased markedly [ IL-2 ： （ 80. 61 ± 18. 63 ） ng/ml vs （770. 99 ± 92. 92 ） ng/ml,P 〈 0.01; IFN-γ： （230.05 ± 47.42） ng/ml vs（984. 19 ± 166. 16） ng/ml, P 〈 0.01 ]. The expression of nuclear factor kappa B decreased significantly as a result of enhancement of inhibitor protein I kappa B. The expression of cytoprotective gene A20 was elevated significantly. Conclusion Prophylactic treatment of recipient with calcitriol following liver transplantation can induce the expression of zinc-finger protein gene A20. As a result, the phospholylation of I kappa B was inhibited and the translocation of NF-κ B was interdicted. Many NF-κB-dependent cytokine such as IL-2 and IFN-gamma were inhibited. In such a way, the acute rejection was inhibited and the recipient survival was prolonged.
出处
《中华普通外科杂志》
CSCD
北大核心
2006年第6期408-410,共3页
Chinese Journal of General Surgery
基金
国家973课题资助项目(2003CB515501)
关键词
肝移植
动物实验
移植物排斥
细胞因子类
锌指蛋白A20
Liver transplantation
Animal experimentation
Graft rejection
Cytokines
Zinc-finger protein A20
