不同原发病的肝移植患者围术期调节性T细胞的变化

Change of Regulatory T Cell in Patients with Different Primary Disease During Perioperation of Liver Transplantation

【目的】探讨因慢性重型肝炎和原发性肝细胞癌(HCC)行肝移植手术患者围术期调节性T细胞免疫功能的变化。【方法】前瞻性选取2008年9月至2010年7月在中山大学附属第三医院因HBV相关性终末期肝病行肝移植手术或肝切除手术患者作为研究对象,剔除术后合并脓毒症、急性排斥反应或手术相关并发症的患者后,分为重型肝炎肝移植组(HSNS组,10例),HCC肝移植组(THC组,10例)和肝癌切除术组(NTHC组,10例),另选取10例健康人作为正常对照组。各组患者分别于术前、术后1、3、7、14 d分别检测外周血T淋巴细胞百分比(T%),CD4+CD25+Foxp3+Treg百分比(Treg%)和Foxp3 mRNA表达。观察其于不同组间的表达水平和术后的变化趋势。【结果】术前HSNS组T%较健康人群明显降低(P<0.0001),Treg%(P<0.0001)和Foxp3 mRNA表达(P=0.002)均显著高于健康人群;THC组与NTHC组Treg%和Foxp3 mRNA表达亦稍高于健康人群,但差异无统计学意义(P>0.05)。另外,HSNS组Treg%显著高于THC组和NTHC组(P<0.001),Foxp3 mRNA表达也分别高于THC组(P=0.006)和NTHC组(P=0.002)。三组患者术后第1天外周血T%显著下降,术后第7天开始回升,并在术后14 d恢复至术前水平,其中NTHC组患者恢复速度较肝移植两组患者迅速。HSNS组术后Treg%和Foxp3 mRNA表达较术前逐渐下降,并在术后第14天与术前比较有显著性差异(P=0.004);THC组术后Treg%和Foxp3mRNA表达也有下降趋势,其中Foxp3 mRNA表达在第14天与术前比较有显著性差异(P=0.019);NTHC组术后Treg%和Foxp3 mRNA在各时间点与术前比较无明显变化(P>0.05)。【结论】HBV感染患者存在不同程度免疫功能下降,而且慢性重型肝炎患者下降程度重于HCC者,术后应结合免疫学指标采取个体化免疫抑制治疗。

[Objective] To investigate the amount and function of regulatory T cell in the patients with chronic severe sepsis or hepatocellular carcinoma in the perioperation of liver transplantation. [ Method] Patients who were underwent liver transplantation or hepateetomy with HBV related end-stage disease from September 2008 to July 2010 were respectively enrolled in this study. Excluded of whom combined with sepsis, acute rejection and surgical related complication, patients were divided into 3 groups： HSNS group （patients with severe hepatitis for liver transplantation, n=l 0）, THC group （patients with HCC for liver transplantation, n=l 0）, and NTHC group （patients with HCC for hepatectomy, n = 10）. Ten healthy volunteer were selected as control group. Percentage of T lymphcyte and CD4＋CD25＋Foxp3＋regulatory T cell （Treg%）, as well as Foxp3 mRNA in peripheral blood were detected at 30 rain pre-transplant and on 1 d, 3 d, 7 d, and 14 d post-transplant. The levels of above parameters and the change trend after transplantation were eompared between three groups. [ Results] Before transplantation, T% in HSNS group was significant lower than volunteers （P 〈 0.0001 ）, while Treg% （P 〈 0.0001 ） and Foxp3 mRNA （P = 0.002） were higher; Treg% and Foxp3 mRNA in THC group and NTHC group were a little higher than control group, but there was no significant difference （P 〉 0.05）. In addition, Treg% in HSNS group was significantly higher than THC group and NTHC group （P 〈 0.001 ）, and Foxp3 mRNA expression was higher than THC group （P = 0.006） and NTHC group （P = 0.002） too. T% in three groups significantly decreased on day 1, began to increase on day 7 post transplant and recovered to the level pre-transplant on day 14. Among the three groups, NTHC group increase more rapidly than the other two groups. The percentage of Treg and Foxp3 mRNA decreased gradually in HSNS group post transplant, and the value on day 14 post transplant was significantly lower than that of pre-transplant （P = 0.004）. The percentage of Treg and Foxp3 mRNA both decreased in THC group post transplant, and Foxp3 mRNA on day 14 post transplant was significantly lower than that of pre- transplant （P = 0.019）. There was no difference of Treg% and Foxp3 mRNA in THC group between post transplant and pre transplant （P 〉 0.05）. [ Conclusion] Patients with HBV infection have weakened immune status. Moreover, the immune status in patients with severe hepatitis was even more weakened than patients with HCC. Individual immunosuppressant therapy should be adopted according to the immunological parameters.