Kobayashi H, Nonami T, Kurokawa T, Takeuchi Y, Harada A, Nakao A, Takagi H
Department of Surgery II, Nagoya University School of Medicine, Japan.
J Surg Res. 1995 Dec;59(6):772-9. doi: 10.1006/jsre.1995.1238.
Evidence has accumulated that oxygen-derived free radicals contribute to the cellular damage induced by ischemia-reperfusion. It has been suggested that nitric oxide (NO) may act as a protective factor in ischemia-reperfusion injury since NO increases blood flow and may scavenge oxyradicals. Nevertheless, controversy exists as to the role of NO. This study was designed to clarify the role of endogenous NO in ischemia-reperfusion-induced liver injury in rats in vivo. Wistar rats weighing 250-300 g were divided into three groups: (1) untreated group (Control); (2) NG-nitro-L-arginine, a specific inhibitor of NO production (L-NNA); and (3) L-arginine-pretreated L-NNA group (AR+L-NNA). Occlusion of all vessels to the median and left hepatic lobes (60 min) was followed by reperfusion for 1 or 24 hr. L-NNA was administered before ischemia as a 10 mg/kg bolus. L-Arginine was given just before L-NNA administration as a 100 mg/kg bolus. Administration of L-NNA resulted in endothelial cell injury characterized by the elevation of serum hyaluronic acid as well as the reduction of hepatic tissue blood flow, and the recovery of hepatic adenosine triphosphate was depressed compared with the control after both 1 and 24 hr of reperfusion. Furthermore, the leakages of various liver enzymes and lipid peroxide were also increased, associated with histological damage. This effect of L-NNA was completely abolished by pretreatment with L-arginine. These results suggest that endogenous NO provides a protective effect against ischemia-reperfusion injury in rat liver.
越来越多的证据表明，氧衍生的自由基会导致缺血再灌注引起的细胞损伤。有人提出，一氧化氮（NO）可能在缺血再灌注损伤中起到保护作用，因为NO可增加血流量并可能清除氧自由基。然而，关于NO的作用仍存在争议。本研究旨在阐明内源性NO在大鼠体内缺血再灌注诱导的肝损伤中的作用。将体重250 - 300 g的Wistar大鼠分为三组：（1）未处理组（对照组）；（2）NO产生的特异性抑制剂NG-硝基-L-精氨酸（L-NNA）组；（3）L-精氨酸预处理的L-NNA组（AR + L-NNA）。对肝中叶和左叶的所有血管进行阻断（60分钟），然后再灌注1或24小时。在缺血前以10 mg/kg的推注剂量给予L-NNA。在给予L-NNA之前，以100 mg/kg的推注剂量给予L-精氨酸。给予L-NNA导致内皮细胞损伤，表现为血清透明质酸升高以及肝组织血流量减少，并且在再灌注1小时和24小时后，与对照组相比，肝三磷酸腺苷的恢复受到抑制。此外，各种肝酶和脂质过氧化物的泄漏也增加，并伴有组织学损伤。L-精氨酸预处理完全消除了L-NNA的这种作用。这些结果表明，内源性NO对大鼠肝脏的缺血再灌注损伤具有保护作用。
