动物造模,帕金森病 z-bio 2022-09-08 261

　　Objective To dynamically evaluate the clinical characteristics of Parkinson's disease systemic models in cynomolgus monkeys using behavioral and molecular imaging methods, and to provide a stable and effective PD primate model for preclinical research on drugs and stem cells.

　　Methods Seven healthy cynomolgus monkeys aged 10-15 years were given continuous intravenous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (1-methyl-4-phenyl-1,2,3 , 6-tetrahydropyridine, MPTP) 0.2mg/kg body weight, induced a systemic PD model, continued to observe the progression of PD symptoms for 3 months, and then gave levodopa intervention. The severity of clinical symptoms of animals was evaluated by PD scoring scale, changes in voluntary movement distance and movement trajectory were analyzed by EtheVision animal trajectory tracking system, and positron emission tomography (PET) molecular imaging agent was used" F-AV-133 assesses the functional status of striatal dopaminergic neurons.

　　Results All animals developed typical PD symptoms including tremor, muscle rigidity and bradykinesia 14 days after MPTP injection, and the clinical score reached a peak (21.43±5.35) at 1 month. Afterwards, PD symptoms tended to be stable, and the clinical scores were significantly increased (P< 0.05). At 3 months, the voluntary movement distance (809.77±401.15) cm was significantly lower than the baseline (8627.46±5751.04) cm (P<0.01). "F-AV-133 bilateral striatal mean specific uptake rate (Sur)) was significantly decreased (P < 0.01) at 3 months (0.16 ± 0.03) compared to baseline (1.66 ± 0.58). After the intervention, PD symptoms were significantly improved, the clinical score (12.86±3.63) was significantly lower than that in the model period (P<0.05), and the voluntary movement distance was significantly increased (P<0.05).

　　Conclusion The PD cynomolgus monkey systemic model constructed in this study has sustained and stable clinical symptoms, striatal dopaminergic nerve damage, effective for L-Dopa intervention, and no spontaneous recovery in the whole process. It more closely simulates the clinical characteristics of PD in vivo dynamics. , in order to provide experimental basis for future research on PD.