Suzuki S, Toledo-Pereyra L H, Rodriguez F J, Cejalvo D
Surgical Research Institute, Borgess Medical Center, Kalamazoo, Michigan 49001.
Transplantation. 1993 Jun;55(6):1265-72. doi: 10.1097/00007890-199306000-00011.
To examine the role of neutrophils, their presence and the degree of infiltration, as important determinants of ischemia and reperfusion injury of the liver, male Sprague-Dawley rats were subjected to 60 and 90 min of total-liver ischemia. The presence of neutrophils, assessed by the measurement of liver tissue myeloperoxidase (MPO), and the degree of neutrophil liver infiltration, determined by the naphthol AS-D chloroacetate esterase technique, correlated well with animal survival and response to FK506 and cyclosporine administration. Lipid peroxidation, measured by the malondialdehyde (MDA) test in liver tissue, was another factor closely linked with liver function and survival. Pretreatment with FK506 (0.3 mg/kg) and CsA (5 mg/kg) was given at 4 hr and 1 hr before ischemia and at the time of reperfusion. Control ischemic animals showed increased neutrophil liver infiltration, high MPO and MDA liver levels, and diminished overall survival. FK506 and CsA-treated animals had better survival and diminished neutrophil liver infiltration, as well as MPO and MDA levels. The mechanism by which FK506 and CsA protected the animals from severe liver ischemic injury is unknown. Our data indicated that the presence and the degree of infiltration of neutrophils were important components of liver ischemia/reperfusion injury in the rat. So it is possible that one of the fundamental effects of the FK506 and CsA might be through the inhibition of the presence and infiltration of neutrophils in liver tissue.
为研究中性粒细胞的作用及其存在情况和浸润程度作为肝脏缺血再灌注损伤的重要决定因素，对雄性Sprague-Dawley大鼠进行60分钟和90分钟的全肝缺血处理。通过测量肝组织髓过氧化物酶（MPO）评估中性粒细胞的存在情况，采用萘酚AS-D氯乙酸酯酶技术确定中性粒细胞在肝脏中的浸润程度，这与动物存活率以及对FK506和环孢素给药的反应密切相关。通过肝组织丙二醛（MDA）检测测量的脂质过氧化是另一个与肝功能和存活率密切相关的因素。在缺血前4小时和1小时以及再灌注时给予FK506（0.3mg/kg）和环孢素A（CsA，5mg/kg）进行预处理。对照缺血动物显示中性粒细胞在肝脏中的浸润增加、肝组织MPO和MDA水平升高以及总体存活率降低。接受FK506和CsA治疗的动物存活率更高，中性粒细胞在肝脏中的浸润减少，MPO和MDA水平也降低。FK506和CsA保护动物免受严重肝脏缺血损伤的机制尚不清楚。我们的数据表明，中性粒细胞的存在和浸润程度是大鼠肝脏缺血/再灌注损伤的重要组成部分。因此，FK506和CsA的基本作用之一可能是通过抑制中性粒细胞在肝组织中的存在和浸润。
