帕金森病食蟹猴系统性模型 z-bo 2020-12-09 422

　　Objective To apply behavioral and molecular imaging methods to dynamically evaluate the clinical characteristics of a systemic model of Parkinson's disease in cynomolgus monkeys, and to provide a stable and effective PD primate model for preclinical studies of drugs and stem cells. Methods Seven healthy cynomolgus monkeys aged 10-15 were given continuous intravenous injections 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 given levodopa intervention. The PD score scale was used to evaluate the severity of the animal’s clinical symptoms, the EtheVision animal trajectory tracking system was used to analyze the distance of voluntary movement and the changes in the trajectory, and the molecular imaging agent of Positron emission tomography (PET) was used. F-AV-133 assesses the functional status of striatal dopaminergic neurons.

　　 Results All animals showed typical PD symptoms including tremor, muscle stiffness, and retardation of movement 14 days after MPTP injection, and the clinical score reached the peak value (21.43±5.35) at 1 month. Subsequently, PD symptoms stabilized and were observed continuously for 2 months (18.43±3.87) and 3 months (18.14±3.53). Compared with the end of MPTP injection (14.43±1.90), the clinical scores were significantly increased (P< 0.05). In 3 months, the distance of voluntary movement (809.77±401.15) cm was significantly lower than that of baseline (8627.46±5751.04) cm (P<0.01). "The average specific uptake rate (Sur) of F-AV-133 bilateral striatum at 3 months (0.16±0.03) was significantly lower than baseline (1.66±0.58) (P<0.01). After L-Dopa was administered 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 distance of voluntary movement was significantly increased (P<0.05). Conclusion The clinical symptoms of the cynomolgus monkey systemic model constructed in this study remain stable, the striatal dopaminergic nerve damage, is effective for L-Dopa intervention, and there is no spontaneous recovery throughout the course, which more closely simulates the clinical characteristics of PD in vivo , In order to provide experimental basis for future research of PD.