Involvement of Adhesion molecules and oxygen free radicals in microcirculatory disturbance in ischemia-reperfusion injury of the liver

本研究旨在探讨粘附分子和氧自由基在肝脏缺血再灌注损伤中的作用。结果：[检查1]1)PGE1或抗ICAM-1治疗组ALT和AST明显降低。PGE1显著增加胆汁产量。它们在中性粒细胞缺失的大鼠中也有所减少。2) IL-8不受PGE1和抗icam -1抗体的影响。3) PGE1、抗icam -1或中性粒细胞缺失大鼠均显著降低了荧光标记透明质酸的保留率。【检查2】再灌注后，对照组贴壁白细胞逐渐显著增加，而PGE1和抗icam -1组无明显增加。[检查3]流式细胞术检测LFA-1和Mac-1的表达不受PGE1的影响。PGE1可抑制内皮细胞的ICAM-1表达。[检查4]PGE1可降低肝细胞和内皮细胞的氧自由基。结论：黏附分子在肝再灌注损伤中起关键作用。中性粒细胞粘附内皮细胞引起缺血再灌注后微循环紊乱。PGE1通过抑制ICAM-1表达，减少中性粒细胞与内皮细胞的粘附，从而保护肝脏免受损伤。

The AIM of this study is to investigate the involvement of adhesion molecules and oxigen free radicals in ischemia-reperfusion injury of the liver. RESULTS: [Exam 1] 1) ALT and AST were significantly decreased by PGE1 or anti ICAM-1 administration. PGE1 increased the bile production significantly. They were also decreased in neutrophil depleted rats. 2) IL-8 was not influenced by administration of PGE1 nor anti-ICAM-1 antibody. 3) The retention rate of fluorescence labeled hyaluronic acid was significantly decreased by PGE1, anti-ICAM-1 administration or in neutrophil depleted rats. [Exam 2] After reperfusion adherent leukocytes had progressively increased significantly in Control group but not in PGE1 and anti-ICAM-1 group. [Exam 3] The expression of LFA-1 and Mac-1 by flow cytometric study was not affected by PGE1. However ICAM-1 on endothelium was suppressed by PGE1 administration. [Exam 4] Oxygen free radicals derived from hepatocytes and endothelium were decreased by PGE1 administration. CONCLUSION: These data indicate that adhesion molecules plays a pivotal role in liver injury after reperfusion. Neutrophil adhesion to endothelial cells caused microcirculatory disturbance after ischemia- reperfusion. PGE1 protects against liver injury through the reduction of neutrophil-endothelial cell adhesion by supression of ICAM-1 expression.