ALPHA-LIPOIC ACID UPREGULATES SIRT1-DEPENDENT PGC-1 alpha EXPRESSION AND PROTECTS MOUSE BRAIN AGAINST FOCAL ISCHEMIA

作者：Fu B; Zhang J; Zhang X^*; Zhang C; Li Y; Zhang Y; He T; Li P; Zhu X; Zhao Y; Zhang Y; Wang X

来源：Neuroscience, 2014, 281: 251-257.

DOI：10.1016/j.neuroscience.2014.09.058

• ischemic stroke
• oxidative stress
• alpha-lipoic acid
• silent mating-type information regulation 2 homolog 1
• peroxisome proliferator-activated receptor-gamma co-activator-1 alpha

Background and object: Silent mating type information regulation 2 homolog 1 (SIRT1) is a class III histone deacetylase and activates peroxisome proliferator-activated receptor-gamma co-activator-1 alpha (PGC-1 alpha) which attenuates oxidative damage. Alpha-lipoic acid (ALA) has been proven to protect the rat brain against cerebral ischemia injury by reducing oxidative stress. However, the underlying mechanisms are poorly understood. In this study, we investigated the potential neuroprotection and the possible role of ALA in SIRT1 pathway.
Methods: Male CD-1 mice were randomly assigned to three groups: Sham, permanent middle cerebral artery occlusion (pMCAO) and ALA group (ALA, 50 mg/kg). ALA was administered intraperitoneally 30 min prior to ischemia in the ALA group. Neurological deficit, infarct volume, and brain edema were detected at 24 h after cerebral ischemia. Immunohistochemistry, western blot and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression of SIRT1 and PGC-1 alpha. Activities of superoxide dismutase (SOD) were measured by assay kits.
Results: Compared with the pMCAO group, the ALA group significantly ameliorated neurological deficit, lessened infarct volume and brain edema, increased the expression of SIRT1, PGC-1 alpha and activities of SOD (P < 0.05).
Conclusions: ALA protected the mouse brain against ischemic damage, and this protection may be through up-regulating SIRT1-dependent PGC-1 alpha expression.

• 出版日期2014-12-5
• 单位河北医科大学