Natori S, Fujii Y, Kurosawa H, Nakano A, Shimada H
Second Department of Surgery, Yokohama City University, Yokohama, Kanagawa, Japan.
Transplantation. 1997 Dec 15;64(11):1514-20. doi: 10.1097/00007890-199712150-00002.
This study investigates the protective mechanism of prostaglandin E1 (PGE1) against hepatic ischemia-reperfusion injury in vivo. It has been demonstrated that activated leukocytes contribute to ischemia-reperfusion injury, and that administration of the monoclonal antibody (mAb) for adhesion molecules reduces the injury by inhibiting leukocyte-endothelial cell adhesion. We therefore attempted to find out whether PGE1 has an effect on the inhibition of neutrophil adherence to endothelial cells after reperfusion.
We administered anti-intercellular adhesion molecule 1 (ICAM-1) mAb, antiserum against rat polymorphonuclear leukocytes, or PGE1 to a rat model of left lobar ischemia for 60 min followed by reperfusion. Leukocyte adherence was observed by intravital fluorescence microscopy. The effect of PGE1 on the expression of adhesion molecules was analyzed by immunohistochemistry and flow cytometry.
Ischemia-reperfusion caused endothelial dysfunction and hepatocellular injury with leukostasis in postsinusoidal venules. Anti-ICAM-1 mAb administration or leukopenia ameliorated both the hepatocellular injury and endothelial dysfunction. Although PGE1 administration did not affect the serum interleukin-8 level, it significantly decreased hepatic injury and leukostasis in the reperfused liver. Immunohistochemical findings showed that PGE1 decreased ICAM-1 expression on endothelial cells, but did not affect lymphocyte function-associated antigen 1, and membrane attack complex 1 on neutrophils in flow cytometric analysis.
We conclude that PGE1 protects the liver against ischemia-reperfusion injury by reducing leukocyte-endothelial cell adhesion via down-modulation of ICAM-1 expression on the endothelium.
本研究在体内探究前列腺素E1（PGE1）对肝缺血再灌注损伤的保护机制。已证实活化的白细胞会导致缺血再灌注损伤，且给予黏附分子单克隆抗体（mAb）可通过抑制白细胞与内皮细胞的黏附来减轻损伤。因此，我们试图弄清楚PGE1在再灌注后对抑制中性粒细胞与内皮细胞黏附是否有作用。
我们将抗细胞间黏附分子1（ICAM-1）mAb、抗大鼠多形核白细胞抗血清或PGE1给予左叶缺血60分钟后再灌注的大鼠模型。通过活体荧光显微镜观察白细胞黏附情况。采用免疫组织化学和流式细胞术分析PGE1对黏附分子表达的影响。
缺血再灌注导致内皮功能障碍和肝细胞损伤，并伴有肝血窦后小静脉内白细胞淤滞。给予抗ICAM-1 mAb或造成白细胞减少可改善肝细胞损伤和内皮功能障碍。尽管给予PGE1不影响血清白细胞介素-8水平，但它可显著减轻再灌注肝脏的损伤和白细胞淤滞。免疫组织化学结果显示，PGE1可降低内皮细胞上ICAM-1的表达，但在流式细胞术分析中不影响中性粒细胞上的淋巴细胞功能相关抗原1和膜攻击复合物1。
我们得出结论，PGE1通过下调内皮细胞上ICAM-1的表达来减少白细胞与内皮细胞的黏附，从而保护肝脏免受缺血再灌注损伤。
