Li X-C, Ma Y-F, Wang X-H
Liver Transplantation Center of the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangshu, China.
Transplant Proc. 2006 Jun;38(5):1584-7. doi: 10.1016/j.transproceed.2006.02.122.
The objective of this study was to investigate the effect of ischemic preconditioning (IPC) on NF-kappaB activity during reperfusion early after liver transplantation in rats.
Male Sprague-Dawley (SD) rats were used as donors and recipients of orthotopic liver transplantations. The donor liver was stored 2 hours in Ringer's solution at 4 degrees C preimplantation. IPC was performed by clamping of the portal vein and hepatic artery of the donor for 10 minutes followed by reperfusion for 10 minutes before harvesting. At 1, 2, 4, and 6 hours after portal vein reperfusion, graft samples were obtained to determine hepatic levels of NF-kappaB activity, tumor necrosis factor (TNF)-alpha and intercellular adhesion molecule (ICAM)-1. Blood samples were obtained to measure serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH).
After liver transplantation without IPC, serum levels of ALT and LDH increased significantly compared with the sham-operated group. Among the IPC group, serum ALT and LDH decreased significantly. NF-kappaB activity in the graft increased within 6 hours after transplantation. Among the IPC group, NF-kappaB activity was significantly attenuated. Hepatic levels of TNF-alpha and ICAM-1 were significantly elevated in the non-IP group but both were reduced in the IPC group.
IPC downregulated TNF-alpha and ICAM-1 expression in the graft, most likely through decreased NF-kappaB activation, and attenuated neutrophil infiltration after reperfusion.
本研究的目的是探讨缺血预处理(IPC)对大鼠肝移植术后早期再灌注期间核因子κB(NF-κB)活性的影响。
雄性Sprague-Dawley(SD)大鼠作为原位肝移植的供体和受体。供体肝脏在植入前于4℃的林格氏液中保存2小时。IPC通过夹闭供体门静脉和肝动脉10分钟,然后在摘取前再灌注10分钟来进行。在门静脉再灌注后1、2、4和6小时,获取移植肝组织样本以测定肝组织中NF-κB活性、肿瘤坏死因子(TNF)-α和细胞间黏附分子(ICAM)-1的水平。采集血样以检测血清丙氨酸转氨酶(ALT)和乳酸脱氢酶(LDH)。
未进行IPC的肝移植术后,与假手术组相比,血清ALT和LDH水平显著升高。在IPC组中,血清ALT和LDH显著降低。移植肝组织中NF-κB活性在移植后6小时内升高。在IPC组中,NF-κB活性显著减弱。非IPC组肝组织中TNF-α和ICAM-1水平显著升高,但在IPC组中两者均降低。
IPC下调了移植肝组织中TNF-α和ICAM-1的表达,最可能是通过降低NF-κB的激活,并减轻了再灌注后的中性粒细胞浸润。