动物造模,帕金森病食蟹猴系统性模型 z-bio 2021-02-23 549

　　Objective: To apply behavioral and molecular imaging methods to dynamically evaluate the clinical characteristics of cynomolgus monkey Parkinson's disease model, and provide a stable and effective PD primate model for preclinical studies of drugs and stem cells.

　　Method: Maintain 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (1-methyl-4-phenyl-1, 2,3), I injected it intravenously. 6-Tetrahydropyridine, MPTP) 0.2 mg/kg body weight, induced a systemic PD model, continued to monitor the progression of PD symptoms for 3 months, and then levodopa intervention. The PD score scale is used to assess the severity of animal clinical symptoms, the EtheVision animal motion track tracking system is used to analyze random travel distance and track changes, and positron emission tomography (positron emission tomography, PET). ) The imaging agent "F-AV-133" evaluates the functional status of striatal dopaminergic neurons.

　　Result: All animals shivered and their muscles were stiff 14 days after MPTP injection. The clinical score reached its peak at 1 month and showed typical PD symptoms, such as slow movement. After (21.43±5.35), PD symptoms were stable, respectively for 2 months (18.43±3.87) and 3 months (2 months (18.43±3.87)). 18.14±3.53) Continue to observe; compared with the termination of MPTP injection (14.43±1.90), the clinical scores were significantly increased (P\u003c0.05). At 3 months (P\u003c0.01), the spontaneous movement distance (809.77) ± 401.15 cm was significantly shorter than the baseline (8627.46 ± 5751.04) cm. -AV-133 average bilateral striatum. Specific intake (Sur) (0.16±0.03) at 3 months was significantly lower than the baseline (1.66±0.58) (P\u003c0.01). After L-dopa intervention, PD symptoms were significantly improved, the clinical score (12.86±3.63) was significantly lower than the model period (P\u003c0.05), and the voluntary exercise distance was significantly increased (P\u003c0.05) P\u003c0. 05).

　　Conclusion: The clinical performance of the whole body PD cynomolgus monkey model constructed in this study remains stable. Striatal dopaminergic nerve damage is effective for L-dopa intervention, and the dynamics of spontaneous recovery of PD during the whole process is more closely simulated . It is expected to provide an experimental basis for future PD research.