Method for establishing monkey systematic Parkinson's disease model

Abstract

The invention discloses a method for establishing a monkey systematic Parkinson's disease model. 0.2mg / kg of MPTP is slowly injected into the vein of lower extremity of a monkey at a flow rate of 1ml / min once daily and is continuously injected for 10-13 days, and the injection is stopped when the Kurlan clinical score is more than or equal to 10; at 3-12 days after the injection is stopped, if the Kurlan scale clinical behavior score is more than or equal to 15 and is stable for at least three months, a stable monkey systematic Parkinson's disease model is obtained; the monkey is a middle-aged and elderly cynomolgus monkey. The cynomolgus monkeys with individual differences and big individual differences can be established into a stable Parkinson's disease model; the obtained monkey systematic Parkinson's disease model can not spontaneously recover; the modeling process and characteristics are similar to the course of primary Parkinson's disease, so a stable model carrier can be provided for the Parkinson's disease pathogenesis study, the pharmacodynamics study and other translational medicine preclinical studies.

Description

technical field [0001] The invention relates to a method for establishing an animal disease model, in particular to a method for establishing a monkey systemic Parkinson's disease model. Background technique [0002] Parkinson's disease is a chronic disease of the central nervous system that affects the activity of patients, and it mostly occurs in middle-aged and older people. The main manifestations of the disease in the early stage include resting tremor, muscle rigidity, slow movement, difficulty in starting movements, and abnormal posture. Resting tremor, uncontrollable shaking of the patient's hands or arms, that occurs at rest or worsens with emotional stress; other early symptoms include difficulty starting activities, followed by frequent tremors in the arms and legs, and loss of fine motor movements in the upper extremities , so that daily life cannot take care of themselves, such as difficulty in dressing, taking off shoes, and washing. The incidence rate of thi...

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Problems solved by technology

[0004] Nevertheless, in addition to the typical pathological characteristics and species differences in the currently applied non-human primate MPTP PD model, there are still the following limitations, which limit its application: (1) Large individual differences, The sensitivity of different individual monkeys to MPTP is different. Given the same dose of MPTP, the response of each animal is very different, and the severity of symptoms varies, making it difficult to compare between different studies; (2) In mild to moderate damage The model is prone to spontaneous recovery, which is inconsistent with the characteristics of progressive aggravation of PD. It lacks prospective and effective prediction of whether the model will spontaneously recover. Previous studies have mostly focused on the simulation of a certain stage of the model. However, there is a lack of overall research on the entire process of the model's clinical evolution and outcome, which is of great significance for the prediction and judgment of the model's clinical evolution, outcome, and selective application; (3) Due to the limited number of aged monkeys, most of the models are Use younger monkeys, and the onset of PD is mostly after middle age, and studies have shown that older monkeys are less likely to spontaneously recover after MPTP modeling than younger monkeys; (4) MPTP The model is not chronic progressive damage. The application of relatively acute MPTP leads to acute damage, which cannot fully simulate the characteristics of slow progressive progression of PD

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