抗黏附分子单克隆抗体对大鼠肝脏缺血再灌注损伤的保护作用。

Protective effect of monoclonal antibodies to adhesion molecules on rat liver ischemia-reperfusion injury.

作者信息

Marubayashi S, Oshiro Y, Maeda T, Fukuma K, Okada K, Hinoi T, Ikeda M, Yamada K, Itoh H, Dohi K

机构信息

Department of Surgery, Hiroshima University School of Medicine, Japan.

出版信息

Surgery. 1997 Jul;122(1):45-52. doi: 10.1016/s0039-6060(97)90263-4.

DOI:10.1016/s0039-6060(97)90263-4

PMID:9225914

Abstract

BACKGROUND

The source of reactive oxygen species in the liver remains to be elucidated. The present study was undertaken to determine whether polymorphonuclear neutrophils (PMNs) can contribute to hepatic ischemia-reperfusion injury, and pretreatment with monoclonal antibodies (mAbs) to intercellular adhesion molecule-1 (ICAM-1), lymphocyte function associated antigen-1 (LFA-1), and CD 18 could improve energy metabolism and prolong the viability of the organ.

METHODS

Male Wistar rats were used. Rat liver ischemia was induced by clamping blood vessels supplying median and left lateral hepatic lobes. Monoclonal antibodies to ICAM-1, LFA-1, or CD18 were injected intravenously 5 minutes before inducing ischemia. To determine the effect of mAbs on the survival rate, total hepatic ischemia was induced by clamping the hepatic artery, portal vein, and bile duct after making a portafemoral shunt.

RESULTS

Although ischemia of the liver for 90 minutes did not permit survival of the animals, pretreatment with mAbs to ICAM-1 plus LFA-1 increased the survival rate to 57%. Pretreatment with mAb to ICAM-1 failed to increase the survival rate. The number of PMNs in the liver increased continually up to 24 hours after reperfusion after 90 minutes of ischemia, and the expression of ICAM-1 was enhanced 4 hours after reperfusion. This is accompanied by a low recovery of hepatic adenosine triphosphate and, on the contrary, a marked increase in lipid-peroxide in the reperfused liver. Pretreatment with mAbs suppressed the infiltration of PMNs and the elevation of lipid peroxide and enhanced the recovery of hepatic adenosine triphosphate 6, 12, or 24 hours after reperfusion. Pretreatment with mAbs also prevented the rise in serum alanine aminotransferase level after reperfusion.

CONCLUSIONS

These results suggest that PMNs contribute to ischemia-reperfusion injury in the liver 4 hours and more after reperfusion, and pretreatment with mAbs to adhesion molecules is useful for the prevention of ischemic liver cell injury.

摘要

背景

肝脏中活性氧的来源仍有待阐明。本研究旨在确定多形核中性粒细胞（PMN）是否会导致肝缺血再灌注损伤，以及用针对细胞间黏附分子-1（ICAM-1）、淋巴细胞功能相关抗原-1（LFA-1）和CD18的单克隆抗体（mAb）进行预处理是否能改善能量代谢并延长器官的存活时间。

方法

使用雄性Wistar大鼠。通过夹闭供应肝中叶和左外叶的血管诱导大鼠肝脏缺血。在诱导缺血前5分钟静脉注射针对ICAM-1、LFA-1或CD18的单克隆抗体。为了确定单克隆抗体对存活率的影响，在进行门腔分流后夹闭肝动脉、门静脉和胆管诱导全肝缺血。

结果

尽管肝脏缺血90分钟后动物无法存活，但用针对ICAM-1加LFA-1的单克隆抗体预处理可将存活率提高到57%。用针对ICAM-1的单克隆抗体预处理未能提高存活率。缺血90分钟后再灌注，肝脏中PMN的数量在再灌注后24小时内持续增加，再灌注后4小时ICAM-1的表达增强。这伴随着肝三磷酸腺苷的低恢复，相反，再灌注肝脏中的脂质过氧化物显著增加。用单克隆抗体预处理可抑制PMN的浸润和脂质过氧化物的升高，并在再灌注后6、12或24小时增强肝三磷酸腺苷的恢复。用单克隆抗体预处理还可防止再灌注后血清丙氨酸转氨酶水平升高。