Effect of paeoniflorin on motor behavior and dopamine neurons of mice with Parkinson's disease by activating autophagy / 中华神经医学杂志

ABSTRACT

Objective:To observe the effect of paeoniflorin on motor behavior and dopamine neurons of mice with Parkinson's disease (PD) by activating autophagy.Methods:Forty C57BL/6 mice were randomly divided into normal control group, model group, paeoniflorin group and paeoniflorin+3-methyl adenine (3-MA) group ( n=10). The later 3 groups were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetmhydropyridine (MPTP) at a dosage of 30 mg/(kg·d) for a consecutive 7 d to establish subacute PD models. Meanwhile, mice in the paeoniflorin group and paeoniflorin+3-MA group were intraperitoneally injected with paeoniflorin (30 mg/[kg·d]) or paeoniflorin (30 mg/[kg·d])+3-MA (2 mg/[kg·d]), respectively. Eight d after modeling, pole test and traction test were used to evaluate the locomotor ability of mice in each group. Then, the substantia nigra of the midbrain was taken; TUNEL was used to detect the nerve cell apoptosis; immunohistochemical staining was used to detect the number of tyrosine hydroxylase (TH) positive cells and the expressions of α-synuclein (α-Syn), lysosomal associated membrane protein 2A (LAMP2A) and microtubule-associated protein 1 light chain 3-II (LC3-II); Western blotting was used to detect the LAMP2A and LC3-II protein levels. Results:As compared with model group, paeoniflorin group had significantly shortened rod climbing time, significantly higher scores in traction test, significantly decreased number of apoptotic nerve cells, significantly increased number of TH-positive cells and expressions of LAMP2A and LC3-II, significantly decreased α-Syn expression, and significantly increased protein levels of LAMP2A and LC3-II ( P<0.05). The paeoniflorin+3-MA group had significantly prolonged rod climbing time, significantly lower scores in traction test, significantly increased number of apoptotic nerve cells, significantly decreased number of TH-positive cells and expressions of LAMP2A and LC3-II, significantly increased expression of α-Syn, and significantly decreased protein levels of LAMP2A and LC3-II as compared with the paeoniflorin group ( P<0.05). Conclusion:Paeoniflorin can improve dyskinesia in PD mice by inducing autophagy to remove α-Syn and protect dopaminergic neurons.