趋化因子IP10及其受体CXCR3早期诊断肝移植术后急性排异

Study on the role of chemokine IP10 and chemokine receptor CXCR3 for prediction of early acute rejection after liver transplantation

目的 探讨趋化因子IP10及其受体CXCR3动态变化与肝移植排斥的关系及其在早期诊断中的意义.方法 以2005年4月-2005年9月在长征医院行肝移植术的30例患者为研究对象,检测患者术前及术后不同时间血清中IP10和外周血淋巴细胞CXCR3的表达,确诊为急性排斥的患者,于当天以及经激素冲击治疗后不同时间分别检测治疗前后患者血清中IP10 和外周血淋巴细胞CXCR3的表达变化. 结果肝移植术前1d （acute rejection, AR）组和（non-acute rejec tion, NAR）组患者血清IP10和外周血淋巴细胞CXCR3的表达与肝癌肝硬化组相比无明显差异（ P＞0.05）,但与正常对照组相比有显著差异（P＜0.01）.肝移植后,AR组、NAR组手术后I P10和外周血淋巴细胞CXCR3的表达均有上升,术后3 d血清中趋化因子水平与术前1d的表达水平相比较,有显著差别（P＜0.05）.NAR组在常规的免疫抑制治疗后5～7 d内下降至术前水平,但AR患者术后不但各个检测时间血清IP10和外周血淋巴细胞CXCR3的表达明显高于NAR组,且在NAR组的表达降低至术前水平6 d后仍然持续高表达,在手术后11 d、12 d 以及术后14 d分别确诊排斥的发生,而当AR组经冲击治疗逆转后,趋化因子IP10表达也相应下降并保持较低水平.结论 血清中趋化因子IP10和外周血淋巴细胞CXCR3的表达与排斥反应密切相关,可作为诊断急性排斥反应的发生,以及观察抗排异疗效的参考指标.

Objective To evaluate the role of chemokine IP10 and chemokine receptor CXCR3 for prediction of early acute rejection after liver transplantation. Methods Thirty cases of liver transplantation performed in April to September 2005 in ChangZbeng Hospital were observed on the changes of chemikines and receptor expression. With ELISA assay and flow cytometry（FCM）, IP10 in serum and CXCR3 expressed on peripheral blood lymphocytes（PBL） were measured on one day before and different times after liver transplantation. In a- cute rejection （AR） group, patients were also studied the changes of chemokines and its receptor expression at different time after anti-rejection therapy, Results Before operation, no significant difference of chemokines and receptor expression among the AR group, NAR group or liver cancer （cirrhosis） group（ （P （0.05）, however, there were significant difference s when it was compared with normal group. The expressions of IP10 and CXCR3 were markedly increased in AR and NAR group 3 days after liver transplantation（ P 〈0.05）. Under the common immunosuppressive therapy, the chemokines and its receptor expression in NAR group patients were decreased to the level of pre-transplantation within 5 - 7 days, however, the expression of chemokines and receptor in AR group patients were not only markedly higher than that in NAR group at different time-point （ P 〈0.01）, but also maintained at higher level to be diagnosed as acute rejection on 11 days, 12 days or 14 days after transplantation. In response to anti-rejection therapy, chemokines and receptor expression were decreased and maintained at lower level in these AR patients. Conclusion Expression of IP10 and CXCR3 in liver transplantation patients are valuable laboratory indices for the prediction of early acute rejection, and are sensitive in response to anti-rejection therapy.