Reiter Russell J, Sainz Rosa M, Lopez-Burillo Silvia, Mayo Juan C, Manchester Lucien C, Tan Dun Xian
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78229, USA.
Ann N Y Acad Sci. 2003 May;993:35-47; discussion 48-53. doi: 10.1111/j.1749-6632.2003.tb07509.x.
This review summarizes the numerous reports that have documented the neuroprotective actions of melatonin in experimental models of ischemia/reperfusion injury (stroke). In these investigations, which have used three species (rat, gerbil, and cat), melatonin was universally found to reduce brain damage that normally occurs as a consequence of the temporary interruption of blood flow followed by the reflow of oxygenated blood to the brain. The exogenous administration of melatonin in these experimental stroke models reduced infarct volume, lowered the frequency of apoptosis, increased the number of surviving neurons, reduced reactive gliosis, lowered the oxidation of neural lipids and oxidatively damaged DNA, induced bcl-2 gene expression (the activity of which improves cell survival), upregulated excision repair cross-complementing factor 6 (an essential gene for preferential DNA excision repair), restrained poly(ADP ribose) synthetase (which depletes cellular NAD resulting in the loss of ATP) activity, and improved neurophysiologic outcomes. Under no circumstances did melatonin exacerbate the damage associated with ischemia/reperfusion injury. As well as the beneficial pharmacologic actions of melatonin, several studies show that a relative deficiency of endogenous melatonin exaggerates neural damage due to stroke; this suggests that even physiologic concentrations of melatonin normally serve to protect the brain against damage. The primary action to explain melatonin's protective effects may relate to its ubiquitous direct and indirect antioxidative actions, although other beneficial functions of melatonin are not precluded.
本综述总结了众多记录褪黑素在缺血/再灌注损伤（中风）实验模型中的神经保护作用的报告。在这些使用了三种动物（大鼠、沙鼠和猫）的研究中，普遍发现褪黑素可减少因脑部血流暂时中断后再灌注含氧血液而通常发生的脑损伤。在这些实验性中风模型中外源性给予褪黑素可减少梗死体积、降低凋亡频率、增加存活神经元数量、减少反应性胶质增生、降低神经脂质氧化和氧化损伤的DNA、诱导bcl-2基因表达（其活性可提高细胞存活率）、上调切除修复交叉互补因子6（优先DNA切除修复的必需基因）、抑制聚（ADP核糖）合成酶（其消耗细胞内NAD导致ATP丧失）的活性，并改善神经生理结果。在任何情况下，褪黑素都不会加重与缺血/再灌注损伤相关的损害。除了褪黑素有益的药理作用外，多项研究表明内源性褪黑素相对缺乏会加剧中风所致的神经损伤；这表明即使是生理浓度的褪黑素通常也有助于保护大脑免受损伤。尽管不排除褪黑素的其他有益功能，但解释其保护作用的主要作用可能与其普遍存在的直接和间接抗氧化作用有关。
