Young C S, Palma J M, Mosher B D, Harkema J, Naylor D F, Dean R E, Crockett E
Department of Surgery, College of Human Medicine, Michigan State University, East Lansing 48824-1315, USA.
Am Surg. 2001 Aug;67(8):737-44.
Neutrophil adhesion and recruitment represents one of the early cellular events that occur during hepatic ischemia/reperfusion (IR) injury and plays a critical role in determining the extent of tissue damage. The adhesion molecules, such as selectins and intercellular adhesion molecules (ICAM), are important in mediating neutrophil-endothelial cell interactions and neutrophil emigration. The goal of this study was to evaluate the role of P-selectin and ICAM-1 in hepatic IR injury. Male wild-type and P-selectin/ICAM-1-deficient (P/I null) mice underwent 90 minutes of partial hepatic ischemia followed by reperfusion at various time points (0, 1.5, 3, and 6 hours). Reperfusion caused a time-dependent hepatocellular injury in both wild-type and P/I null mice as judged by plasma alanine aminotransferase (ALT) levels and liver histopathology examination. Although ALT levels were slightly lower in the P/I null mice compared with the wild-type mice the differences were not statistically significant. Neutrophil infiltration to the ischemic liver was observed in both mouse groups after 6 hours of reperfusion; however, the infiltration to the midzonal region of the ischemic liver was more pronounced in the wild-type group. This study suggests that hepatocellular injury induced after hepatic IR was independent of P-selectin and ICAM-1 in this model of acute inflammatory tissue injury.
中性粒细胞的黏附和募集是肝缺血/再灌注（IR）损伤过程中早期发生的细胞事件之一，在决定组织损伤程度方面起着关键作用。黏附分子，如选择素和细胞间黏附分子（ICAM），在介导中性粒细胞与内皮细胞相互作用以及中性粒细胞迁移中起重要作用。本研究的目的是评估P-选择素和ICAM-1在肝IR损伤中的作用。雄性野生型和P-选择素/ICAM-1缺陷（P/I缺失）小鼠经历90分钟的部分肝缺血，随后在不同时间点（0、1.5、3和6小时）进行再灌注。根据血浆丙氨酸转氨酶（ALT）水平和肝脏组织病理学检查判断，再灌注在野生型和P/I缺失小鼠中均导致了时间依赖性的肝细胞损伤。虽然与野生型小鼠相比，P/I缺失小鼠的ALT水平略低，但差异无统计学意义。再灌注6小时后，在两个小鼠组中均观察到中性粒细胞浸润到缺血肝脏；然而，野生型组中缺血肝脏中区区域的浸润更为明显。本研究表明，在这种急性炎症组织损伤模型中，肝IR后诱导的肝细胞损伤与P-选择素和ICAM-1无关。
