Melatonin prevents lipopolysaccharide-induced hyporeactivity in rat
Melatonin prevents lipopolysaccharide-induced hyporeactivity in rat
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DOI：
10.1046/j.1600-079x.2003.00111.x
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发表时间：
2004-04-01
影响因子：
10.3
通讯作者：
Sorrentino, R
中科院分区：
文献类型：
--
作者：
Bianca, RDD;Marzocco, S;Sorrentino, R
褪黑素（MT）是松果体的主要分泌产物，其作为免疫调节剂的作用已经得到了很好的证实。最近有证据表明，MT对感染性休克、失血性休克和炎症均有保护作用。来自大肠杆菌的脂多糖（LPS）直接给予动物刺激许多细胞和系统产生各种炎症介质。脂多糖引起的感染性休克的特点是低血压和血管对收缩剂的低反应性。特别是，活性氧如超氧化物和一氧化氮（NO）参与脓毒性休克的病理生理。在这项研究中，我们证明了MT预处理可以防止体内和内毒素处理大鼠主动脉环对苯肾上腺素的低反应性。MT的有益作用似乎与其抗氧化特性和抑制主动脉诱导型一氧化氮合酶（iNOS）蛋白表达、减少NO生成和硝基酪氨酸形成、防止血管和内皮损伤有关。此外，我们首次证明，MT抑制核酶聚合（adp -核糖）合成酶在维管组织中的激活。目前的研究强调了MT对感染性休克相关血管功能障碍的保护作用，这些数据可以支持MT在人类内毒素血症中的临床应用。
Melatonin (MT) is the principal secretory product of the pineal gland and its role as an immumo-modulator is well established. Recent evidence shows that MT exerts protective effects in septic shock, hemorrhagic shock and inflammation. Lipopolysaccharide (LPS), from Escherichia coli, administered to animals directly stimulates a number of cells and systems to produce various inflammatory mediators. LPS-induced septic shock is characterized by hypotension and vascular hyporeactivity to contracting agents. In particular, the reactive oxygen species such as superoxide and nitric oxide (NO) contribute to the pathophysiology of septic shock. In this study, we demonstrate that MT pretreatment prevents the hyporeactivity to phenylephrine in vivo and in aorta rings collected from rats treated with the endotoxin. The beneficial effect of MT seems related to its antioxidant properties and with inhibition of inducible nitric oxide synthase (iNOS) protein expression, reduction of NO production and nitrotyrosine formation, in aorta, preventing vascular, and endothelial injury. Additionally, we first demonstrate, that MT inhibited nuclear enzyme poly (ADP-ribose) synthetase activation in vascular tissue. The current study underlined the protective effect of MT on the vascular dysfunction associated with septic shock, data that could support the clinical use of MT in human endotoxemia.