CAJ | 학술논문

目的通过大鼠移植肝在不同冷保存时间再灌注后核因子-κB(nuclear transcription factor-κB, NF-κB)及其相关炎性因子的激活情况,判断冷保存时间、NF-κB激活以及移植肝功能损伤三者之间的联系.方法用Wistar大鼠建立原位肝移植模型,假手术组(A组)作为对照组,观察大鼠移植肝在4 ℃ UW液中保存45 min(B组)、120 min(C组)、180 min(D组)以及再灌注3 h后肝组织、血清中NF-κB、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和肝损伤指标丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和肝细胞凋亡的变化情况.结果随着移植肝冷保存时间的延长NF-κB逐渐激活(P<0.05),并使肝组织内TNF-α、IL-1β水平上调(P<0.05);再灌注后,NF-κB近一步激活(P<0.05),肝组织中TNF-α、IL-1β进一步上调(P<0.05),ALT、AST和肝细胞凋亡指数明显升高(P<0.05),肝功能损害加重.结论 NF-κB在供肝的冷保存阶段随时间的延长呈诱导性激活,再灌注后呈爆发式激活,并通过上调其靶基因TNF-α、IL-1β的转录产生肝脏损伤,这可能是肝脏冷保存再灌注损伤发生的重要机制.
목적 통과대서이식간재불동랭보존시간재관주후핵인자-κB(nuclear transcription factor-κB, NF-κB)급기상관염성인자적격활정황,판단랭보존시간、NF-κB격활이급이식간공능손상삼자지간적련계.방법 용Wistar대서건립원위간이식모형,가수술조(A조)작위대조조,관찰대서이식간재4 ℃ UW액중보존45 min(B조)、120 min(C조)、180 min(D조)이급재관주3 h후간조직、혈청중NF-κB、종류배사인자-α(TNF-α)、백세포개소-1β(IL-1β)화간손상지표병안산전안매(ALT)、천동안산전안매(AST)화간세포조망적변화정황.결과 수착이식간랭보존시간적연장NF-κB축점격활(P<0.05),병사간조직내TNF-α、IL-1β수평상조(P<0.05);재관주후,NF-κB근일보격활(P<0.05),간조직중TNF-α、IL-1β진일보상조(P<0.05),ALT、AST화간세포조망지수명현승고(P<0.05),간공능손해가중.결론 NF-κB재공간적랭보존계단수시간적연장정유도성격활,재관주후정폭발식격활,병통과상조기파기인TNF-α、IL-1β적전록산생간장손상,저가능시간장랭보존재관주손상발생적중요궤제.
Objective To establish a model of rat orthotopic liver transplantation and investigate the relationship among cold preservation time, activation of nuclear transcription factor-κB (NF-κB) and donor preservation injury after liver transplantation. Methods Orthotopic liver transplantation was performed in Wistar rats which were randomly divided into the following groups according to the different duration of liver cold storage in UW solution: group A (sham operation, n=10), group B NF-κB in liver before and after transplantation was measured by electrophoretic mobility shift assays; protein expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in the liver was measured by immunohistochemistry; the serum TNFα and IL-1β, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic cell apoptosis were examined. Results With extended cold storage duration, the activity of NF-κB in the donor liver increased (P<0.05, group D vs. groups A, B and C). TNF-α and IL-1β levels also increased (P<0.05, group D vs. groups A, B and C). Donor liver reperfusion injury was gradually aggravated with the prolonging of graft cold preservation. Both the serum TNF-α and IL-1β levels increased highly (P<0.05 group A vs. groups B, C and D),NF-κB in the liver significantly increased (P<0.05, group A vs. groups D, B and C) with gradual prolonging of graft cold preservation time. The serum ALT and AST level and apoptosis index level elevated greatly (P<0.05, group A vs. groups D, B and C). Conclusion NF-κB of donor liver was activated inductively in cold preservation phase and activated explosively in reperfusion phase. The longer cold preservation time was, the higher NF-κB level in donor liver became. NF-κB led to the expression of TNF-α and IL-1β in donor liver. Inflammatory factors are one of the most important mechanisms for the donor liver injury after liver transplantation.