羟墓自由基引起神经细胞［Ca^（2＋）］i增高的机制和Ebselen的抑制作用

MECHANISM OF THE ENHACEMENT OF HYDROXYL RDICALS ON [Ca￣(2+)]i IN RAT CEREBRAL CORTICAL NEURONAL CELLS AND THE INHIBITION OF EBSELEN

用Ｆｕｒａ－２显微荧光测量技术研究了羟基自由基对单个皮层神经细胞内游离钙离子浓度［Ｃａ２＋］ｉ影响和硒化合物Ｅｂｅｌｅｎ对［Ｃａ２＋］ｉ的抑制作用。结果表明羟基自由基的作用首先引起胞内［Ｃａ２＋］ｉ以时间常数τ＝３８９５．４±５０７．２Ｓ速度缓慢增加，然后加入了以τ＝４２０．６±１２２．０Ｓ的外钙大量涌入。钙通道阻断剂、疏基还原剂、疏基还原制和自由基清除剂对羟基自由基损伤作用的影响提示外钙的大量涌入部分与通道的开放有关，疏基损伤在羟基自由基引起的［Ｃａ２＋］ｉ升高中起着重要的作用。具有类谷胱甘肽过氧化酶活性的小分子硒化合物Ｅｂｓｅｌｅｎ（１０－５ｍｏｌ／Ｌ和１０－６ｍｏｌ／Ｌ）抑制羟基自由基引起的［Ｃａ２＋］ｉ升高，推测它可以抑制钙库的释放或促进内钙的外排以及抑制外钙的流入。

The mechanism of the enhancement effect of hydroxyl radicals on [Ca2+]i in single rat cerebral conical neuronal cells and the inhibition of Ebselen was studied by using Fura-2 microfluorometric technique. The results show that the hydroxyl radicals cause a slow increase with time constant (τ)=3895.4±507.2S and then join a quick influx of extracellular Ca2+ with τ=420.6±122.0S. The influences of calcium channel antagonist, sulfhydryl reductive agent and free radical scavenger on the increase of [Ca2+]i induced by hydroxyl radicals suggest that the influx of extracellular Ca2+ partly relates to the opening of calcium channels and the damage of sulfhydryl makes a great contribution to this hydroxyl radical-induced increase.Ebselen, with glutathione peroxidase-fore activity in vitro, shows and inhibition on the increase of [Ca2+]i induce by hydroxyl radicals and is probably through inhibiting the Ca2+ release from calcium pool, promoting the exflux of inhacellular Ca2+ and inhibiting the influx of extracellular Ca2+ as well.