期刊
CRITICAL CARE MEDICINE
卷 38, 期 4, 页码 1147-1154出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0b013e3181cd124e
关键词
shock; endothelial dysfunction; resveratrol; nicotinamide adenine dinucleotide phosphate oxidase; reactive oxygen species; estrogen receptor; hemeoxygenase-1
资金
- National Science Council [NSC95-2320-B-182-030-MY3, EMRPD170331, NSC 96-2314-B-182A017-MY2]
- Chang Gung Memorial Hospital [CMRPF170101, CMRPG360901, CMRPG360902]
Objective: To determine whether resveratrol provides vasculo-protection in trauma-hemorrhaged animals and whether the effects are mediated via estrogen receptor-dependent hemeoxygenase-1. Design: Prospective, multiexperimental, randomized, controlled studies. Setting: University research laboratory. Subjects: Male Sprague-Dawley rats weighing 300-350 g. Interventions: Male Sprague-Dawley rats underwent trauma hemorrhage (mean arterial pressure 40 mm Hg for 90 min, then resuscitation). Resveratrol (30 mg/kg) with or without an estrogen receptor antagonist (ICI 182,780), a hemeoxygenase enzyme inhibitor (chromium-mesoporphyrin), or vehicle was injected during resuscitation. At 24 hrs after trauma hemorrhage with resuscitation or sham operation, the animals were euthanized for further evaluation. Measurements and Main Results: Acetylcholine-induced endothelium- dependent relaxation decreased, whereas nicotinamide adenine dinucleotide-stimulated superoxide radical production in the aorta and aortic p22phox, p47phox, gp91phox, NOX1, and NOX4 mRNA concentrations increased in trauma-hemorrhaged rats vs. sham rats. All altered parameters were normalized in resveratrol-treated trauma-hemorrhaged rats. Furthermore, there was a significant increase in hemeoxygenase-1 after trauma hemorrhage, and resveratrol treatment further increased hemeoxygenase-1 expression in trauma-hemorrhaged rats. However, administration of ICI 182,780 or chromium-mesoporphyrin abolished the resveratrol-induced prevention of shock-induced oxidative stress and endothelial damage. In the resveratrol-treated rats subjected to trauma hemorrhage, there were significant improvements in plasma aspartate aminotransferase and alanine aminotransferase levels, and mortality rate, and there was lesser damage in histology. Conclusions: Resveratrol treatment prevented the overproduction of superoxide radical/NADPH oxidase expression and restored the trauma- hemorrhage-impaired endothelium-dependent relaxation via estrogen receptor-dependent stimulation of hemeoxygenase-1 expression. (Crit Care Med 2010; 38: 1147-1154)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据