Ebselen对自由基诱发的皮层神经元和皮层线粒体脂质过氧化损伤的保护作用  

PROTECTION OF EBSELEN ON OXYGEN FREE RADICAL INDUCED LIPID PEROXIDATION DAMAGE OF CULTURED RAT CORTICAL NEURON AND CORTICAL MITOCHONDRIA

作　　者：谈冶雄[1] 李万亥[1] 姜远英[1] 陶学斌[1] 陈卫平[1] 

机构地区：[1]第二军医大学药学院

出　　处：《药学学报》1997年第3期166-170,共5页Acta Pharmaceutica Sinica

摘　　要：观察了ｅｂｓｅｌｅｎ对超氧阴离子Ｏ·－２和羟自由基·ＯＨ诱发的体外培养大鼠皮层神经元乳酸脱氢酶（ｌａｃｔｉｃｄｅｈｙｄｒｏｇｅｎａｓｅ，ＬＤＨ）释放，和ＴＢＡＲＳ（ｔｈｉｏｂａｒｂｉｔｕｒｉｃａｃｉｄｒｅａｃｔｉｖｅｓｕｂｓｔａｎｃｅ）含量升高及制备的皮层线粒体ＴＢＡＲＳ含量升高的影响。结果表明：超氧阴离子和羟自由基引起了培养神经元和线粒体明显的损伤。浓度在５～５０μｍｏｌ·Ｌ－１之间，ｅｂｓｅｌｅｎ能剂量依赖性地抑制ＬＤＨ释放和ＴＢＡＲＳ含量的增加，对线粒体的ＴＢＡＲＳ含量升高也有显著的抑制作用。但浓度为０．２～５０μｍｏｌ·Ｌ－１时，药物无直接清除超氧阴离子和羟自由基的活性。因此，ｅｂｓｅｌｅｎ对氧自由基诱发的神经元脂质过氧化损伤有拮抗作用，这种作用与直接清除自由基无关。Ebselen(2 phenyl 1,2 benzisoselenanzol 3(2H) one, C 13 H 9NOSe) is a seleno organic anti oxidant compound. In this study, the effect of ebselen on lipid peroxidation damage induced by O ·- 2 and ·OH in vitro , of cultured rat cortical neuron and cortical mitochondria was studied. When neuron was exposed to hypoxanthine/xathine oxidase system and vitamin C/CuSO 4 system, obvious damage was dectected: lactic dehydrogenase(LDH)was released and TBARS content increased. Ebselen(10,25,50 μmol·L -1 ) reduced LDH efflux induced by O ·- 2 and ·OH in a dose dependent manner. As for the TBARS content, from 5 μmol·L -1 to 50 μmol·L -1 , ebselen negated its increase, also dose dependently. Furthermore, ebselen lowered TBARS content of cortical mitochondria treated with O ·- 2 and ·OH in a dose related manner. But ebselen showed no activity of scavenging O ·- 2 and ·OH. This suggests that ebselen has direct anti oxidant activity on neuron and its activity is not achieved by scavenging oxygen free radical.

关 键 词：EBSELEN 抗氧化活性 皮层 神经元 线粒体 自由基 

分 类 号：R977.9[医药卫生—药品]