肝脏移植再灌注损伤早期NF-κB活性的影响及意义

Effect of Ischemia Reperfusion Injury on Nuclear Factor-κB Activation during Early Stage Following Liver Transplantation

目的观察肝脏移植后再灌注早期血液核转录因子-κB(NF-κB)活性、TNF-α、肝酶学指标的关系,探讨再灌注早期再灌注损伤的机制。方法对20例肝硬化晚期病人(实验组)接受肝移植术前1h,供肝恢复血供后1、2、4及6h抽取患者外周血进行肝酶学检查,用Westernblot技术检测外周血中NF-κBP65表达,用双抗体夹心酶联免疫吸附法测定外周血中TNF-α表达水平,同时与10例健康成人(对照组)外周血肝酶学指标、NF-кBP65和TNF-α水平对比。结果肝移植术后早期外周血肝酶学指标在4h达到高峰,4h后呈现下降趋势,NF-κBP65和TNF-α的表达水平在2h达到峰值,且均高于移植术前和对照组,差异均有统计学意义(P<0.05)。结论NF-кBP65及TNF-α在肝移植术后早期高表达,同时伴有肝脏损伤酶学指标反应性上调,表示肝移植术后肝脏炎症通路活跃,可能和缺血后再灌注有关。

Objective To study the effect s of ischemic reperfusion injury on the activity of nuclear factor-κB （NF-κB） and the expressions of TNF-α,ALT and AST from peripheral blood during early stage following liver transplantation.Methods Twenty patients of late stage hepatic cirrhosis defined as the experiment group, the blood samples were harvestd at 1h before live transplantation, at 1h, 2h、4h and 6h followed by donator live blood recovery, respectively; ten healthy adults were defined as the control group. The NF-κB P65 relative level of blood was detected by Western blot analysis and the TNF-α level of blood was detected by ABC enzyme linked immunosorbent assay. Serum ALT and AST were also measured.Results The expression level of serum ALT and AST of peripheral blood rised to the peak level in 4h,then showed the descending trend;the level of NF-κB p65 and TNF-α were rised to the peak level in 2h,then showed the descending trend, which were higher than that before transplantation and those of the control group（P〈0.01）.Conclusion The higher expression of TNF-α P65 and TNF-α in the early stage after liver transplantation following up-relagution of serum ALT and AST suggested inflammatory pathway was activated after liver transplation, which should be explained by ischemia reperfusion injury.