Abstract: Objective To observe the effects of butylphthalide on depressive behavior and the expression of NOD-like receptor protein 3 (NLRP3) and ionised calcium binding adaptor molecule 1 (IBA-1) in the substantia nigra striatum of mice with Parkinson's disease (PD) and depression. Methods Forty male adult C57 mice were divided into normal control group (n=10) and model group (n=30). The model group was given intraperitoneal injection of MPTP first, and then given chronic unpredictable mild stress to construct the PD combined with depression model. Among the 30 model mice, 10 mice were not treated (PD with depression group), 10 mice were administered with metopar (6.25 mg/kg) for one week (metopar group), and the other 10 mice were administered with metopar (6.25 mg/kg) combined with butylphthalide (120 mg/kg) for one week ( metopar combined with butylphthalide group). The behavior of mice was evaluated by forced swimming test, tail hanging test and sugar water preference test. The expression of NLRP3 and IBA-1 in the substantia nigra striatum was detected by Western Blot. Immunofluorescence was used to observe the activation of microglia and the damage of dopamine neurons in the substantia nigra striatum. Results Compared with normal control group, the forced swimming rest time and tail suspension rest time in PD with depression group were prolonged, the preference rate of sugar water was decreased, and the expression of NLRP3 and IBA-1 was increased, with statistically significant differences (all P<0.05). Compared with PD with depression group, the forced swimming resting time and suspended tail resting time were shortened, the sugar water preference rate was increased, and the expression of NLRP3 and IBA-1 was decreased in metobar group and metobar combined with butylphthalide group, especially in metobar combined with butylphthalide group, with statistical differences (all P<0.05). Compared with normal control group, the number of abnormally activated microglia in PD with depression group was significantly increased, the cell body was enlarged and the axon was decreased; The number of dopamine neurons was decreased, and the cell body was atrophied. Compared with PD with depression group, the number of activated microglia was significantly decreased and the number of dopamine neurons was increased in tmedoba combined with butylphthalide group. Conclusions Butylphthalide can improve the depressive symptoms of PD mice with depression by inhibiting the activation of microglia and inflammatory bodies, and reducing the inflammatory response.

Key words: Parkinson's disease, depression, butyphthalide, NOD-like receptor protein 3, microglia