Abstract: Objective To investigate the effect of butylphthalide on apoptosis of hippocampal neurons in rats with Alzheimer's disease (AD). Methods The rats were divided into control group, AD model group and the rats were intraperitoneally injected with D-galactose and aluminium trichloride, the low, medium and high dose groups of butylphthalide (25, 50 and 100 mg/kg) were given intragastric administration, 12 rats in each group. Flow cytometry was used to detect the apoptosis of hippocampal neurons, HE was used to observe the morphological changes of hippocampal CA1 neurons, real-time-PCR was used to detect the expression of Tau protein and apoptotic factors Bcl-2, Bax and caspase-3 mRNA in hippocampal neurons, and Western blot was used to detect the expression of mTOR, AKT and GSK-3β in hippocampal neurons. Results Compared with the control group, the escape latency and the first time to find the original platform of model group were significantly prolonged, the number of times to cross the original platform was significantly reduced, and the apoptotic rate of hippocampal neurons was significantly increased, and the expression of Tau, Bax and caspase-3 mRNA increased, while the expression of Bcl-2 mRNA and mTOR, AKT and GSK-3β decreased in the model group (P < 0.05). Compared with the model group, the escape latency and the first time to find the original platform in the low, medium and high dose butylphthalide groups were significantly shortened in the 3rd to 5th day, the number of times to cross the original platform was significantly increased, and the apoptotic rate of hippocampal neurons was significantly reduced, and the expression of Tau, Bax and caspase-3 mRNA decreased, while the expression of Bcl-2 mRNA and mTOR, AKT and GSK-3β increased (P<0.05). Conclusions Butylphthalide can significantly inhibit the apoptosis of hippocampal neurons in AD rats, its mechanism may be related to inhibition of Tau protein, regulation of apoptosis factors and activation of mTOR/AKT/GSK-3β signaling pathway.

Key words: Alzheimer's disease, Butylphthalide, Hippocampal neurons, MTOR/AKT/GSK-3β signaling pathway