Vega V L, Maldonado M, Mardones L, Schulz B, Manrïquez V, Vivaldi E, Roa J, Ward P H
Department of Physiopathology, Universidad de Concepción, Chile.
Shock. 1999 Jun;11(6):403-10.
Küpffer cells (KCs) have been implicated in leukocyte recruitment and microvascular dysfunction associated with liver inflammation. The overall objective of this study was to assess the role of KCs and polymorphonuclear (PMN) leukocytes on the oxidative stress elicited in the liver as a consequence of hind limb reperfusion in rats subjected to tourniquet shock, a shock model that differs from other models in that hepatic injury is a consequence of remote organ damage. Colloidal carbon clearance from blood and its incorporation into KCs demonstrate that these cells are activated after the 2 h hind limb reperfusion period and that they are responsible for the observed oxidative stress and for PMN leukocyte recruitment and activation. Liver oxidative stress in this model is evidenced by increased liver tissue GSSG/GSH ratio, thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, myeloperoxidase (MPO) activity, an index of tissue-associated neutrophil accumulation, and a significant loss in total tissue superoxide dismutase (SOD) activity. Mean arterial blood pressure (MAP), as well as plasma levels of alanine aminotransferase (ALT), an index of hepatic tissue injury, total SOD activity, plasma levels of alpha-tocopherol and beta-carotene, and total plasma nitrite are also affected as a consequence of KC activation after the 2 h hind limb reperfusion period. Inhibition of KC activity by gadolinium chloride (GdCl3) reverted most of the above alterations to values that do no differ from those found in control animals. These results support the hypothesis that hepatic and systemic oxidative stress elicited by hind limb reperfusion in rats subjected to tourniquet shock is both KC and PMN leukocyte dependent.
库普弗细胞（KCs）与白细胞募集以及肝脏炎症相关的微血管功能障碍有关。本研究的总体目标是评估KCs和多形核（PMN）白细胞在大鼠后肢再灌注导致的肝脏氧化应激中所起的作用，该后肢再灌注是在止血带休克的大鼠中进行的，这一休克模型与其他模型不同之处在于肝损伤是远程器官损伤的结果。血液中胶体碳清除率及其在KCs中的掺入表明，这些细胞在2小时后肢再灌注期后被激活，并且它们是观察到的氧化应激以及PMN白细胞募集和激活的原因。该模型中肝脏氧化应激的证据包括肝组织GSSG/GSH比值增加、硫代巴比妥酸反应性物质（TBARS，脂质过氧化指标）、髓过氧化物酶（MPO）活性（组织相关中性粒细胞积聚指标）以及总组织超氧化物歧化酶（SOD）活性的显著丧失。平均动脉血压（MAP）以及丙氨酸转氨酶（ALT，肝组织损伤指标）、总SOD活性、血浆α-生育酚和β-胡萝卜素水平以及总血浆亚硝酸盐水平，在2小时后肢再灌注期后由于KC激活也受到影响。氯化钆（GdCl3）抑制KC活性可使上述大多数改变恢复到与对照动物无差异的值。这些结果支持这样的假设，即止血带休克大鼠后肢再灌注引发的肝脏和全身氧化应激既依赖于KC也依赖于PMN白细胞。
