缺血预处理对大鼠肝脏移植物再灌注早期NF-κB活性的影响及意义

Effect of Ischemic Preconditioning on Nuclear Factor-κB Activation During Early Reperfusion Following Orthotopic Liver Transplantation in Rats

目的观察缺血预处理对大鼠肝脏移植后再灌注早期核转录因子-κB(NF-κB)活性和TNF-α、细胞间黏附分子-1(ICAM-1)表达的影响,探讨缺血预处理的保护机理。方法建立大鼠肝脏移植模型,供肝在林格液中保存2h,实验分假手术组、对照组和缺血预处理组(IP组)3组,IP组于供肝切取前夹闭第一肝门10min,然后开放10min。分别于移植再灌注后1、2、4及6h抽血进行肝酶学检查,切取肝脏作NF-κB活性、TNF-α和ICAM-1表达的测定。结果IP组肝功能得到有效改善。与假手术组比较,对照组及IP组再灌注后移植物的NF-κB活性明显增强,且在1、2h达高峰,4h后减弱,TNF-α和ICAM-1表达也随之增加;同对照组相比,IP组的NF-κB活性降低,并且在1、2h差异具有统计学意义(P<0.05),TNF-α和ICAM-1表达亦降低。结论缺血预处理对于供肝的保护作用可能是通过抑制再灌注早期NF-κB的活性,减少了TNF-α和ICAM-1炎症介质的释放,从而减轻了移植物再灌注早期的炎症反应实现的。

Objective To study the effects of ischemic preconditioning （IP） on the activity of nuclear factor- kB （NF-kB） and the expressions of TNF-α and intercellular adhesion molecule-1 （ICAM-1） during early reperfusion following liver transplantation in rats. Methods The models of rat orthotopic liver transplantation were established. The donor livers were stored for 2 hours in Ringers solution at 4 ℃ before transplantation. All rats were randomly divided into sham operation group （SO group）, control group and IP group. IP group was achieved by clamping the portal vein and hepatic artery of donor liver for 10 minutes followed by reperfusion for 10 minutes before harvesting. The activity of NF-kB and expressions of TNF-α and ICAM-1 at 1 h, 2 h, 4 h and 6 h after reperfusion were measured. Serum ALT, LDH were also determined. Results The liver function of recipients with IP were significantly improved. Compared with SO group, the graft NF-kB activity increased after transplantation in control group and IP group （P〈0.05）, while compared with control group that was significantly attenuated at 1 h and 2 h in IP group. Similarly, hepatic levels of TNF-α and ICAM-1 were significantly elevated in control group and were reduced in IP group. Conclusion IP might down-regulated TNF-α and ICAM-1 expression in the grafts after orthotopic liver transplantation through depressed NF-kB activation, and attenuate neutrophil infiltration in the grafts after reperfusion.