ROLE OF NITRIC-OXIDE IN THE OXIDANT STRESS DURING ISCHEMIA REPERFUSION INJURY OF THE LIVER
ROLE OF NITRIC-OXIDE IN THE OXIDANT STRESS DURING ISCHEMIA REPERFUSION INJURY OF THE LIVER
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DOI：
10.1016/0024-3205(92)90064-v
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发表时间：
1992-01-01
期刊：
影响因子：
6.1
通讯作者：
FARHOOD, A
中科院分区：
文献类型：
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作者：
JAESCHKE, H;SCHINI, VB;FARHOOD, A
在雄性 Fischer 大鼠体内肝缺血再灌注损伤模型中研究了一氧化氮 (NO) 及其与超氧化物、过氧亚硝酸盐的反应产物的潜在作用。 用NO合酶抑制剂硝基-L-精氨酸（10 mg/kg）进行预处理既不影响初始再灌注阶段的缺血后氧化应激和肝损伤，也不影响随后的中性粒细胞向肝脏的浸润以及后来的中性粒细胞诱导的损伤阶段。 此外，没有发现任何证据表明缺血后亚硝酸盐（NO 的稳定氧化代谢物）尿排泄量增加。 相比之下，给予Fischer大鼠肠炎沙门氏菌内毒素（1mg/kg）可引起显着的利尿作用，尿中亚硝酸盐排泄量增加800倍。 硝基-L-精氨酸预处理可抑制内毒素诱导的亚硝酸盐形成 97%。 肝脏 cGMP 水平（作为肝脏中 NO 形成的指标）仅在施用内毒素后显着升高，而在缺血和再灌注后则不显着升高。 我们的结果没有提供再灌注期间全身或局部NO或过氧亚硝酸盐生成增加的证据，因此这些代谢物中的任何一种不太可能参与肝缺血后再灌注期间的氧化应激和肝损伤。
The potential role of nitric oxide (NO) and its reaction product with superoxide, peroxynitrite, was investigated in a model of hepatic ischemiareperfusion injury in male Fischer rats in vivo. Pretreatment with the NO synthase inhibitor nitro-L-arginine (10 mg/kg) did neither affect the postischemic oxidant stress and liver injury during the initial reperfusion phase nor the subsequent infiltration of neutrophils into the liver and the later, neutrophil-induced injury phase. Furthermore, no evidence was found for a postischemic increase of the urinary excretion of nitrite, a stable oxidation metabolite of NO. In contrast, the administration of Salmonella enteritidis endotoxin (1 mg/kg) induced a significant diuresis in Fischer rats and an 800-fold enhancement of the urinary nitrite excretion. Nitro-L-arginine pretreatment inhibited the endotoxin-induced nitrite formation by 97%. Hepatic cGMP levels, as index of NO formation in the liver, were only increased significantly after endotoxin administration but not after ischemia and reperfusion. Our results provide no evidence for any enhanced generation of NO or peroxynitrite either systemically or locally during reperfusion and therefore it is unlikely that any of these metabolites are involved in the oxidant stress and liver injury during reperfusion after hepatic ischemia.