Kobayashi S, Clemens M G
Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Circ Shock. 1992 Jul;37(3):245-52.
In order to examine the possible contribution of the Kupffer cell to the generation of hypoxia/reoxygenation injury in the liver, primary cultures of hepatocytes, either alone or in coculture with Kupffer cells, were exposed to 90 min of sublethal hypoxia followed by 120 min of reoxygenation. Prolonged incubation of cocultured hepatocytes and Kupffer cells resulted in increased release of lactic dehydrogenase (LDH) indicating cell injury even under normoxic conditions. LDH release was further increased by the presence of Kupffer cells during hypoxia/reoxygenation. To determine whether or not this effect of Kupffer cells might be the result of oxygen-derived free radical production, we assessed the efficacy of the enzymatic scavengers superoxide dismutase (SOD) + catalase in ameliorating the Kupffer cell mediated injury. SOD + catalase was effective in preventing free radical injury generated by hypoxanthine + xanthine oxidase. However, SOD + catalase did not ameliorate hepatocyte injury caused by Kupffer cells. Thus, activation of Kupffer cells may be an important factor in the genesis of liver injury, but the mediator of Kupffer cell exacerbation of hepatocyte injury appears to be a mechanism other than free radicals released into the medium. These results indicate that chemical substances from the activated Kupffer cells may cause hepatocyte damage, which cannot be blocked by SOD + catalase, and suggest that these substances at reflow may be important for the genesis of reperfusion injury in vivo.
为了研究库普弗细胞对肝脏缺氧/复氧损伤发生的可能作用，将原代培养的肝细胞单独培养或与库普弗细胞共培养，使其暴露于90分钟的亚致死性缺氧状态，随后再进行120分钟的复氧。共培养的肝细胞和库普弗细胞长时间孵育导致乳酸脱氢酶（LDH）释放增加，这表明即使在常氧条件下细胞也受到了损伤。在缺氧/复氧过程中，库普弗细胞的存在进一步增加了LDH的释放。为了确定库普弗细胞的这种作用是否可能是氧衍生自由基产生的结果，我们评估了酶性清除剂超氧化物歧化酶（SOD）+过氧化氢酶减轻库普弗细胞介导损伤的效果。SOD+过氧化氢酶可有效预防次黄嘌呤+黄嘌呤氧化酶产生的自由基损伤。然而，SOD+过氧化氢酶并不能改善库普弗细胞引起的肝细胞损伤。因此，库普弗细胞的激活可能是肝损伤发生的一个重要因素，但库普弗细胞加剧肝细胞损伤的介质似乎是一种不同于释放到培养基中的自由基的机制。这些结果表明，活化的库普弗细胞产生的化学物质可能导致肝细胞损伤，而这种损伤不能被SOD+过氧化氢酶阻断，这表明这些物质在再灌注时可能对体内再灌注损伤的发生很重要。
