[依布硒啉对氧自由基诱导的大鼠皮层神经元及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].

作者信息

Tan Y X, Li W H, Jiang Y Y, Tao X B, Chen W P

机构信息

Department of Pharmacy, Second Military Medical College, Shanghai 200433.

出版信息

Yao Xue Xue Bao. 1997;32(3):166-70.

PMID:11327014

Abstract

Ebselen (2-phenyl-1, 2-benzisoselenanzol-3 (2H) one, C13 H9NOSe) is a seleno-organic anti-oxidant compound. In this study, the effect of ebselen on lipid peroxidation damage induced by O2.- 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/CuSO4 system, obvious damage was detected: lactic dehydrogenase(LDH) was released and TBARS content increased. Ebselen (10, 25, 50 mumol.L-1) reduced LDH efflux induced by O2.- and .OH in a dose-dependent manner. As for the TBARS content, from 5 mumol.L-1 to 50 mumol.L-1, ebselen negated its increase, also dose-dependently. Furthermore, ebselen lowered TBARS content of cortical mitochondria treated with O2.- and .OH in a dose-related manner. But ebselen showed no activity of scavenging O2.- and .OH. This suggests that ebselen has direct anti-oxidant activity on neuron and its activity is not achieved by scavenging oxygen free radical.

摘要

依布硒啉（2-苯基-1,2-苯并异硒唑-3(2H)酮，C13H9NOSe）是一种有机硒抗氧化化合物。本研究探讨了依布硒啉对体外培养的大鼠皮层神经元和皮层线粒体中由超氧阴离子（O2.-）和羟自由基（.OH）诱导的脂质过氧化损伤的影响。当神经元暴露于次黄嘌呤/黄嘌呤氧化酶系统和维生素C/硫酸铜系统时，检测到明显损伤：乳酸脱氢酶（LDH）释放，硫代巴比妥酸反应物（TBARS）含量增加。依布硒啉（10、25、50μmol·L-1）以剂量依赖性方式降低了由O2.-和.OH诱导的LDH外流。至于TBARS含量，从5μmol·L-1到50μmol·L-1，依布硒啉也以剂量依赖性方式抑制其升高。此外，依布硒啉以剂量相关方式降低了用O2.-和.OH处理的皮层线粒体的TBARS含量。但依布硒啉没有清除O2.-和.OH的活性。这表明依布硒啉对神经元具有直接抗氧化活性，且其活性不是通过清除氧自由基来实现的。