Abstract:

Objective To assess the impacts of sirolimus（SRL）and tacrolimus（TAC）on immune conditionin renal transplant recipients，in order to find the optimal immunosuppressive regimens. Methods According to the different immunosuppressive regimens，18 living donor renal transplant recipients with stable renal functionwere divided into two groups ：SRL group（n ＝ 8）on SRL + mycophenolate mofetil（MMF）+ prednisone（Pred）and TAC group（n ＝ 10）on TAC + MMF + Pred. All the patients received the immunosuppressive regimens for atleast one year. The living donors were chosen as the blank control. All the subjects of the 3 groups were examined for the proportion of Regulatory T（Treg）cells（CD4+CD25+Foxp3+）and Regulatory B（Breg）cells（CD19+CD5+CD1d+） in their peripheral blood mononuclear cells（PBMCs）by flow cytometry. After stimulation by the corresponding donor's PBMCs，the recipient's PBMCs were measured through the production of interferon-γ（IFN-γ）and interleukin-10（IL-10）of the recipient's PBMCs of SRL group and TAC group were measured by enzyme-linkedimmunospot assay（ELISPOT）. Results The proportion of CD4+ CD25+ Foxp3+ Treg in the SRL group，TACgroup and blank control group were（6.68±0.42）％，（3.59±0.47）％ and（6.59±0.36）％，respectively. The ratio of the SRL group and blank control group were significantly higher than that of the TAC group（both P ＜ 0.05），and there was no statistically significant difference between the SRL group and blank control group（P ＞ 0.05）. Theproportion of CD19+CD5+CD1d+ B cells in the SRL group，TAC group and blank control group were（16.43±3.56）%，（13.09±1.64）％ and（16.58±1.31）％，respectively. There were no statistically significant differences among thethree groups（all P ＞ 0.05）. The frequency of the cellsproducing IFN-γ in the SRL group and TAC group detectedby ELISPOT were（117.00±21.54）/ 500 000 and（126.00±24.08）/ 500 000，without significant difference （P ＞ 0.05）. The frequency of the cellsproducing IL-10 in the SRL group and TAC group were（347.00±55.29）/ 500 000 and（249.00±58.97）/ 500 000，without significant difference（P ＞ 0.05）. Conclusion The regimenbased on SRL shows no effect on the percentage of Treg of PBMC in long-term renal transplant recipients，however， the regimen based on TAC reduces the percentages. Meanwhile，both the regimens have no impact on the proportionof Breg in the peripheral CD19+ B cells and on the donor-specific immune reaction.

摘要：

目的 探讨肝胰十二指肠联合移植的适应证和治疗效果。方法 总结分析本中心近两年实施的肝胰十二指肠联合移植 2 例，1 例为酒精性肝硬化伴 2 型糖尿病，1 例为乙肝肝硬化伴 2 型糖尿病肾病。2 例患者均采用原位整块的肝脏、十二指肠、胰腺联合移植。供者器官切取和修整简单，移植时依次吻合肝上、肝下下腔静脉 ；供者肠系膜上静脉与受者肠系膜上静脉吻合 ；供者腹腔干动脉与受者肝总动脉吻合。术后采用巴利昔单抗诱导治疗；采用他克莫司（FK506）+ 霉酚酸酯（MMF）+ 泼尼松（Pred）三联免疫抑制治疗。结果 患者 1 实施肝胰十二指肠联合移植，术后出现肠瘘，未发生弥漫性腹膜炎和严重感染，经充分引流后，肠瘘逐渐愈合。患者 2 实施肝胰十二指肠移植联合肾移植，术后出现胰腺周围积液和切口愈合不良，予以充分引流和换药处理后痊愈 ；2 例患者术后移植肝和移植胰腺功能恢复正常，完全脱离胰岛素治疗。患者 1 由于术后 1 年 7 个月发生急性排斥反应，应用甲泼尼龙冲击治疗，出现胃肠穿孔继发腹膜炎而死亡 ；患者2 术后 6 个月出现血丙氨酸转氨酶（ALT）升至 150 U/L，转换为低剂量他克莫司联合西罗莫司治疗，患者肝功能改善，ALT 维持在 80 U/L。患者存活至今，移植物功能良好。结论 对于终末期肝病伴有血糖难以控制的糖尿病患者实施肝胰十二指肠联合移植治疗，可以取得良好的治疗效果。

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