内源性辅因子硫辛酸和二氢硫辛酸对纹状体的N-甲基-D-天冬氨酸（NMDA）和丙二酸损伤具有神经保护作用。

The endogenous cofactors, thioctic acid and dihydrolipoic acid, are neuroprotective against NMDA and malonic acid lesions of striatum.

作者信息

Greenamyre J T, Garcia-Osuna M, Greene J G

机构信息

Department of Neurology, University of Rochester Medical Center, NY 14642.

出版信息

Neurosci Lett. 1994 Apr 25;171(1-2):17-20. doi: 10.1016/0304-3940(94)90593-2.

DOI:10.1016/0304-3940(94)90593-2

PMID:8084483

Abstract

Thioctic acid (alpha-lipoic acid) and dihydrolipoic acid are endogenous, interconvertible cofactors of the mitochondrial pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase complexes. These compounds help to maintain glutathione and alpha-tocopherol in their reduced states, and they possess intrinsic free radical scavenging properties. We examined whether systemic treatment with thioctic acid or dihydrolipoic acid is protective against direct- and indirect-acting excitotoxins. Adult rats were treated for 10 days with intraperitoneal injections of vehicle, thioctic acid or dihydrolipoic acid, and on day 7 of treatment animals received unilateral stereotaxic injections of NMDA or malonic acid into the striatum. Histological assessment 3 days after the stereotaxic injections revealed a marked reduction in lesion volume in animals treated with thioctic acid or dihydrolipoic acid. We conclude that thioctic acid and dihydrolipoic acid are neuroprotective against direct and indirect excitotoxic insults.

摘要

硫辛酸（α-硫辛酸）和二氢硫辛酸是线粒体丙酮酸脱氢酶和α-酮戊二酸脱氢酶复合物的内源性、可相互转化的辅因子。这些化合物有助于维持谷胱甘肽和α-生育酚处于还原状态，并且它们具有内在的自由基清除特性。我们研究了用硫辛酸或二氢硫辛酸进行全身治疗是否对直接和间接作用的兴奋性毒素具有保护作用。成年大鼠腹腔注射赋形剂、硫辛酸或二氢硫辛酸，持续治疗10天，在治疗的第7天，动物接受向纹状体内单侧立体定向注射N-甲基-D-天冬氨酸（NMDA）或丙二酸。立体定向注射3天后的组织学评估显示，用硫辛酸或二氢硫辛酸治疗的动物损伤体积明显减小。我们得出结论，硫辛酸和二氢硫辛酸对直接和间接兴奋性毒性损伤具有神经保护作用。