Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
Neurochem Int. 2010 Feb;56(3):495-500. doi: 10.1016/j.neuint.2009.12.009. Epub 2009 Dec 21.
The present study was carried out to elucidate the neuroprotective effect and influence of resveratrol on the extracellular levels of neurotransmitter and neuromodulator during ischemia/reperfusion in rats. Male rats were divided into three groups: sham operation, ischemia treatment, and ischemia combined with resveratrol treatment (resveratrol-treated group, 30 mg/kg intraperitoneally for 7 days). Cerebral ischemia was induced by using the model of middle cerebral artery occlusion. The dialysates in hypothalamus were obtained by brain microdialysis technique. The levels of sixteen amino acids and amines in microdialysate were monitored by capillary electrophoresis analysis. This study shows that the ischemic infarcts were significantly reduced and neurological functions were improved in resveratrol-treated group compared to ischemia group. The analysis results demonstrate that chronic treatment with resveratrol remarkably reduced the release of excitatory neurotransmitter glutamate, aspartate and neuromodulator d-Serine during ischemia and reperfusion; and significantly increased the basal extracellular levels of inhibitory neurotransmitter gamma-amino-n-butyric acid, glycine and taurine. Chronic treatment with resveratrol also ameliorated O-phosphoethanolamine levels and excitotoxic index during ischemia and reperfusion. This study provides the first in vivo evidence that resveratrol could exert neuroprotective effect against ischemia injury by modulating the release of multiple neurotransmitters and neuromodulators during ischemia/reperfusion.
本研究旨在阐明白藜芦醇在大鼠脑缺血/再灌注期间对神经递质和神经调质细胞外水平的影响及其神经保护作用。雄性大鼠分为三组:假手术组、缺血处理组和缺血合并白藜芦醇处理组(白藜芦醇处理组,腹腔内注射 30mg/kg,连续 7 天)。采用大脑中动脉闭塞模型诱导脑缺血。通过脑微透析技术获得下丘脑的透析液。通过毛细管电泳分析监测微透析液中 16 种氨基酸和胺类的水平。本研究表明,与缺血组相比,白藜芦醇处理组的缺血性梗死明显减少,神经功能得到改善。分析结果表明,慢性白藜芦醇处理可显著减少缺血再灌注期间兴奋性神经递质谷氨酸、天冬氨酸和神经调质 D-丝氨酸的释放;并显著增加抑制性神经递质γ-氨基丁酸、甘氨酸和牛磺酸的基础细胞外水平。慢性白藜芦醇处理还可改善缺血再灌注期间 O-磷酸乙醇胺水平和兴奋性毒性指数。本研究首次提供了体内证据,表明白藜芦醇通过调节缺血/再灌注期间多种神经递质和神经调质的释放,发挥其对缺血损伤的神经保护作用。