Abstract:

 Objective   To evaluate the effect and mechanism of L-3-n-butyphthalide(NBP) on amyloid beta-protein 1-42(Aβ1-42)-induced apoptosis in primary cultured cortical neurons through a mitochondrial apoptotic pathway. Methods   After pretreatment with NBP of different concentrations (0.1, 1 and 10μmol/L) for 4h and exposure to Aβ1-42(10μmol/L) for 24h,  changes of cell viability were determined by MTT,  and LDH,  MDA and SOD enzyme activities were spectrophotometrically determined to evaluate oxidative status. Cell morphology was observed by an inverted fluorescence microscope,  and the apoptotic rate was calculated. Expressions of target proteins(Bcl-2,  Bax,  cytochrome C,  caspasce-3 and cleaved caspase-3) were determined by Western blot. Results   After exposure to Aβ1-42 for 24h,  cell viability was remarkably decreased,  while the cell apoptotic rate was increased. The SOD activity was decreased,  while the MDA content and LDH activity were increased. Expressions of Bcl2 and mitochondrial cytochrome C were decreased,  while expressions of Bax,  cytoplasmic cytochrome C,  caspasce-3 and cleaved caspase-3 were increased(P＜0.05). Pretreatment with NBP for 4h significantly inhabited the effects of Aβ1-42(P＜0.05).Conclusion   NBP can inhibit oxidative damage of cortical neurons induced by Aβ1-42, decrease the cell apoptotic rate, and protect neurons through a mitochondrial apoptotic pathway.

Key words: Amyloid beta-protein; Neurons; Alzheimer  disease; Oxidative stress；Mitochondrial apoptotic pathway