帕金森病,动物造模 z-bio 2021-10-13 499

　　Purpose: To apply behavioral and molecular imaging methods to dynamically evaluate the systemic model of cynomolgus Parkinson's disease, to stabilize and effective PD, to conduct preclinical studies of drugs, stem cells and other therapies, so as to provide a primate model.

　　Method: 7 healthy cynomolgus monkeys, aged between 10 and 15 years old, with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (1-methyl-4-benzene Base-1,2), of which 3 kinds of persistent drugs I inject intravenously. , 6-tetrahydropyridine, MPTP) 0.2 mg/kg body weight, induced a systemic PD model, continued to observe the progression of PD symptoms for 3 months, and then intervened with levodopa. The PD score scale is used to assess the severity of animal clinical symptoms, the EtheVision animal orbit tracking system is used to analyze voluntary movement distance and orbit changes, and positron emission tomography (PET) molecular imaging.

　　Results: 14 days after MPTP injection, all animals experienced tremor, muscle stiffness, and movement delay. The clinical score reached a peak at 1 month (21.43±5.35), after which PD symptoms were stable, 2 months (18.43±3.87) and 3 Month (18.14±3.53). Keep watching. Compared with the termination of MPTP injection (14.43±1.90), both clinical scores increased significantly (P\u003c0.05). Voluntary movement distance (809.77±) 401.15) cm. It was significantly lower than the baseline (8627.46±575.1.04) cm (P\u003c0.01) at 3 months. "The uptake (Sur) of the bilateral striatum (0.16±0.03) of F-AV-133 at 3 months was significantly lower than the baseline (1.66±0.58) (P\u003c0.01). After L-dopa intervention, PD symptoms Significant improvement, the clinical score (12.86±3.63) was significantly lower than the model period (P\u003c0.05), and the voluntary travel distance was significantly increased (P). ). ). Conclusion: The PD cynomolgus monkey system model established in this study The clinical manifestations of the striatum remain stable, and the striatal dopaminergic nerve damage is effective for L-dopa intervention, and there is no spontaneous recovery during the entire process. It is expected that the clinical features that mimic the dynamics of PD in vivo will provide an experimental basis for future studies of PD.