他克莫司和雷帕霉素对肝癌肝移植患者Foxp^3＋Treg的影响及防治排斥反应的研究

The effect of FK506 and Rapamycin on the expression of Foxp^3＋ Treg in liver cancer patientsundergoing liver transplant and its clinical relevance

目的探讨免疫抑制剂他克莫司和雷帕霉素对肝癌肝移植受者Foxp^3＋Treg产生的影响及其防治排斥反应的疗效。方法自移植后第2个月到第12个月，每月采血，采用实时荧光定量PER法检测他克莫司组和雷帕霉素组肝癌肝移植受者新鲜外周血单个核细胞中Foxp3mRNA的表达水平，通过同期术后观察和实验室检查，比较两组受者间Foxp3mRNA表达水平和急性排斥反应发生率的差异。结果他克莫司组受者的外周血单个核细胞中Foxp3mRNA表达水平（0．1032±0．0943）明显低于雷帕霉素组受者（1．2136±0．6738），差异有统计学意义（t=5．1610，P〈0．01）；雷帕霉素组患者比同期他克莫司组受者术后急性排斥反应发生率明显减低，差异有统计学意义（x^2=2．2222，P〈0．05）。结论他克莫司抑制了肝癌肝移植术后免疫耐受的诱导，而雷帕霉素可能参与了免疫耐受的诱导和维持；雷帕霉素对肝癌肝移植受者防治排斥反应的效果更好。

Objective To investigate the expression of Foxp^3＋Treg in liver cancer patientsreceiving liver transplant atter immunosuppressive protocols FK506 or Rapamycin and evaluate the rejection prevention. Methods Liver transplant patients were randomly divided into FK506 group （ 10 cases）, and Rapamycin group （10 cases）. Real time quantitatve PCR was used to examine Foxp3 mRNA expression of patients＇ PBMC starting the 2nd month for consecutively 10 months. Foxp3 mRNA and incidences of acute rejection were compared between the two groups. Results Foxp3 mRNA expression was significantly lower in the FK506 group （0. 1032±0. 0943） as compared to that in the Rapamycin group （ 1. 2136 ±0. 6738 ） （t = 5. 1610, P 〈0. 01 ） ;The incidences of acute rejection was significantly lower in the Rapamycin group as compared to that in the FK506 group after operation in the same period （ X^2 = 2. 2222, P 〈 O. 05 ）. Conclusions FK506 may suppress the induction of immune tolerance after liver transplantation, while Rapamycin may play an important role in inducing and maintaining graft immune tolerance. Rapamycin is better than FK506 in preventing rejection reaction in liver cancer patients receiving liver transplant.