Hisama N, Yamaguchi Y, Okajima K, Uchiba M, Murakami K, Mori K, Yamada S, Ogawa M
Department of Surgery II, Kumamoto University Medical School, Japan.
Dig Dis Sci. 1996 Jul;41(7):1481-6. doi: 10.1007/BF02088576.
We investigated whether anticoagulation would diminish ischemia-reperfusion injury of the liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. Anticoagulant was injected intravenously 10 min before occlusion. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, reaching a peak at 6 hr, then decreasing gradually to control levels by 24 hr. CINC levels in rats pretreated with heparin (50 units/kg), AT-III (250 units/kg), or DEGR-Xa (10 mg/kg) peaked at 3 hr after reperfusion and declined to baseline within 12 hr; peak CINC values were significantly lower than in untreated control rats. Expression of CINC mRNA in liver tissue paralleled the CINC serum levels. Both myeloperoxidase activity and the number of neutrophils in the liver were decreased in the anticoagulant groups. In addition, significant correlations were observed between the maximum values of AST, ALT, and LDH versus the peak CINC levels following ischemia-reperfusion. These results indicate that the release of CINC after ischemia-reperfusion of the liver is mediated by activation of coagulation within the hepatic microcirculation.
我们研究了抗凝是否会减轻肝脏的缺血再灌注损伤。通过阻断门静脉30分钟在大鼠中诱导肝脏缺血。在阻断前10分钟静脉注射抗凝剂。未处理大鼠再灌注后血清细胞因子诱导的中性粒细胞趋化因子（CINC）浓度升高，在6小时达到峰值，然后在24小时逐渐降至对照水平。用肝素（50单位/千克）、抗凝血酶III（250单位/千克）或去甘氨酸-精氨酸-凝血因子Xa（10毫克/千克）预处理的大鼠CINC水平在再灌注后3小时达到峰值，并在12小时内降至基线；CINC峰值显著低于未处理的对照大鼠。肝组织中CINC mRNA的表达与CINC血清水平平行。抗凝组肝脏中的髓过氧化物酶活性和中性粒细胞数量均降低。此外，观察到缺血再灌注后谷草转氨酶、谷丙转氨酶和乳酸脱氢酶的最大值与CINC峰值水平之间存在显著相关性。这些结果表明，肝脏缺血再灌注后CINC的释放是由肝微循环内凝血激活介导的。
