Jiang Yong, Gu Xiao-Ping, Qiu Yu-Dong, Sun Xue-Mei, Chen Lei-Lei, Zhang Li-Hua, Ding Yi-Tao
Department of Hepatobiliary Surgery, Gulou Hospital, Medical Department of Nanjing University, Jiangsu Province, China.
World J Gastroenterol. 2003 Sep;9(9):2025-9. doi: 10.3748/wjg.v9.i9.2025.
Polymorphonuclear neutrophil (PMN) plays a major role in liver ischemia/reperfusion injury. Protective effect of ischemic preconditioning (IP) has been confirmed in liver ischemia/reperfusion injury. The purpose of this study was to investigate the effect of IP on C-X-C chemokine expression and PMNs recruitment early after liver transplantation.
Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation (OLT). The donor liver was stored 24 hours in University of Wisconsin (UW) solution at 4 degrees pre-implantation. IP was done by clamp of the portal vein and hepatic artery of the donor liver for 10 minutes followed by reperfusion for 10 minutes before harvesting. The neutrophilic infiltration in liver was quantified using a myeloperoxidase (MPO) assay. Intragraft expression of macrophage inflammatory protein-2 (MIP-2) mRNA was investigated with in situ hybridization. The serum levels of MIP-2 and tumor necrosis factor (TNF)-alpha were also monitored.
After liver transplantation without IP, the hepatic MPO increased significantly compared with sham operated group. In IP group, PMN in liver indicated by MPO was reduced significantly. In situ hybridization showed no MIP-2 mRNA in sham group but dramatic expression in hepatocytes in non-IP group. In IP group, MIP-2 mRNA was significantly down-regulated. Similarly, serum MIP-2 and TNF-alpha levels were significantly elevated in non-IP group and both were reduced in IP group.
IP might protect graft liver from preservation-reperfusion injury after OLT through down-regulating C-X-C chemokine expression of hepatocytes, and alleviating PMNs recruitment after reperfusion.
多形核中性粒细胞（PMN）在肝脏缺血/再灌注损伤中起主要作用。缺血预处理（IP）对肝脏缺血/再灌注损伤的保护作用已得到证实。本研究旨在探讨IP对肝移植术后早期C-X-C趋化因子表达及PMN募集的影响。
雄性Sprague-Dawley大鼠作为原位肝移植（OLT）的供体和受体。供体肝脏在植入前于4℃的威斯康星大学（UW）溶液中保存24小时。IP通过夹闭供体肝脏的门静脉和肝动脉10分钟，然后在摘取前再灌注10分钟来完成。使用髓过氧化物酶（MPO）测定法对肝脏中的中性粒细胞浸润进行定量。用原位杂交法研究移植肝内巨噬细胞炎性蛋白-2（MIP-2）mRNA的表达。还监测了血清中MIP-2和肿瘤坏死因子（TNF）-α的水平。
未进行IP的肝移植术后，与假手术组相比，肝脏MPO显著升高。在IP组中，以MPO表示的肝脏中的PMN显著减少。原位杂交显示假手术组无MIP-2 mRNA，但非IP组的肝细胞中有显著表达。在IP组中，MIP-2 mRNA显著下调。同样，非IP组血清MIP-2和TNF-α水平显著升高，而IP组两者均降低。
IP可能通过下调肝细胞C-X-C趋化因子的表达，并减轻再灌注后PMN的募集，从而保护移植肝脏免受OLT后保存-再灌注损伤。
