Department of Anesthesiology, Chang Gung Memorial Hospital, National Pingtung University of Science and Technology, Pingtung, Taiwan.
Crit Care Med. 2010 Apr;38(4):1147-54. doi: 10.1097/CCM.0b013e3181cd124e.
To determine whether resveratrol provides vasculoprotection in trauma-hemorrhaged animals and whether the effects are mediated via estrogen receptor-dependent hemeoxygenase-1.
Prospective, multiexperimental, randomized, controlled studies.
University research laboratory.
Male Sprague-Dawley rats weighing 300-350 g.
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.
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.
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.
确定白藜芦醇能否为创伤性出血动物提供血管保护作用，以及这种作用是否通过雌激素受体依赖性血红素加氧酶-1 介导。
前瞻性、多实验、随机、对照研究。
大学研究实验室。
雄性 Sprague-Dawley 大鼠，体重 300-350 克。
雄性 Sprague-Dawley 大鼠接受创伤性出血（平均动脉压 40mmHg 持续 90 分钟，然后复苏）。在复苏期间，给予白藜芦醇（30mg/kg）加或不加雌激素受体拮抗剂（ICI 182,780）、血红素加氧酶酶抑制剂（铬中卟啉）或载体。在创伤性出血复苏或假手术后 24 小时，处死动物进行进一步评估。
与假手术大鼠相比，创伤性出血大鼠的乙酰胆碱诱导的内皮依赖性舒张功能降低，而烟酰胺腺嘌呤二核苷酸刺激的主动脉和主动脉 p22phox、p47phox、gp91phox、NOX1 和 NOX4mRNA 浓度增加；创伤性出血大鼠所有改变的参数在白藜芦醇治疗组中均恢复正常。此外，创伤性出血后血红素加氧酶-1 显著增加，白藜芦醇治疗进一步增加了创伤性出血大鼠的血红素加氧酶-1 表达。然而，给予 ICI 182,780 或铬中卟啉可消除白藜芦醇诱导的休克诱导的氧化应激和内皮损伤的预防作用。在接受创伤性出血的白藜芦醇治疗大鼠中，血浆天冬氨酸转氨酶和丙氨酸转氨酶水平、死亡率显著改善，组织学损伤减轻。
白藜芦醇治疗可防止超氧化物阴离子/NADPH 氧化酶表达的过度产生，并通过雌激素受体依赖性血红素加氧酶-1 表达的刺激来恢复创伤性出血损伤的内皮依赖性舒张功能。
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