Construction method of Parkinson's disease animal model

A construction method and technology of Parkinson's disease, applied in the field of construction of animal models of Parkinson's disease, can solve problems such as short administration mode, achieve scientific pathological evaluation, reduce side effects, and increase toxicity

Inactive Publication Date: 2020-02-28
JIANGSU INST OF NUCLEAR MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, high doses of MPTP cannot well mimic the slowly progressive features of human Parkinson's disease due to the rapid toxic kinetics and short dosing pattern
[0007] At present, there is no research at home and abroad to use chemical small molecules to inhibit the activity of VMAT2 and then to investigate the degree of damage to dopaminergic neurons by the neurotoxic substance MPTP.

Method used

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  • Construction method of Parkinson's disease animal model
  • Construction method of Parkinson's disease animal model
  • Construction method of Parkinson's disease animal model

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] 8-week-old C57BL / 6 male mice, clean grade, weighing 20-30 g, were purchased from Changzhou Cavens Experimental Animal Co., Ltd. The weight and vitality of the mice were evaluated, and the mice with obvious listlessness, light weight or heavy weight were excluded, and the qualified mice were adaptively raised in the animal room of Jiangsu Institute of Atomic Medicine. After adaptive feeding for 1 week, they were given joint administration.

[0041] D-dihydrotetrabenazine ((+) DTBZ) was dissolved in 20% DMSO to prepare dihydrotetrabenazine injection, the concentration of dihydrotetrabenazine was 1.25mg / ml, and it was ready for use. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was dissolved in physiological saline to prepare MPTP injection, the concentration of MPTP was 2.5mg / ml, and it was ready for use.

[0042] Weigh each mouse before administration every day, according to the single dose of (+)DTBZ is 5mg / kg mouse, the single dose of MPTP is 10mg / kg mouse, and ...

Embodiment 2

[0045] 8-week-old C57BL / 6 male mice, clean grade, weighing 20-30 g, were purchased from Changzhou Cavens Experimental Animal Co., Ltd. The weight and vitality of the mice were evaluated, and the mice with obvious listlessness, light weight or heavy weight were excluded, and the qualified mice were adaptively raised in the animal room of Jiangsu Institute of Atomic Medicine. After adaptive feeding for 1 week, they were given joint administration.

[0046] Dextrodihydrotetrabenazine ((+) DTBZ) was dissolved in 20% DMSO, and dissolved with hydrochloric acid (the final concentration of hydrochloric acid was 0.036%-0.038%), prepared as dihydrotetrabenazine injection, two Hydrotetrabenazine concentration is 1.25mg / ml, standby. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was dissolved in physiological saline to prepare MPTP injection with a concentration of MPTP of 2.5 mg / ml for use.

[0047] Weigh each mouse before administration every day, according to the single dose of ...

Embodiment 3

[0050] 8-week-old C57BL / 6 male mice, clean grade, weighing 20-30 g, were purchased from Changzhou Cavens Experimental Animal Co., Ltd. The weight and vitality of the mice were evaluated, and the mice with obvious listlessness, light weight or heavy weight were excluded, and the qualified mice were adaptively raised in the animal room of Jiangsu Institute of Atomic Medicine. After adaptive feeding for 1 week, they were given joint administration.

[0051] D-dihydrotetrabenazine ((+) DTBZ) was dissolved in 20% DMSO to prepare dihydrotetrabenazine injection, the concentration of dihydrotetrabenazine was 1.25 mg / ml, and it was ready for use. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was dissolved in physiological saline to prepare MPTP injection, the concentration of MPTP was 2.5mg / ml, and it was ready for use.

[0052] Weigh each mouse before administration every day, according to the single dose of (+) DTBZ is 7.5mg / kg mouse, the single dose of MPTP is 12.5mg / kg mouse...

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Abstract

The invention belongs to the technical field of animal model construction, and relates to a construction method of a Parkinson's disease animal model. The construction method includes the step: integrally applying an inhibitor of a vesicular monoamine transporter II and an environmental neurotoxin to an animal. According to the construction method, the inhibitor of the vesicular monoamine transporter II and the environmental neurotoxin are targeted to the VMAT2 (vesicular monoamine transporter II) and a mitochondrial complex I, the PD (Parkinson's disease) animal model induced by non-single factors is coincident with an etiological idea that a Parkinson's disease is induced by multi-factors, and characteristics of human Parkinson's diseases can be more effectively simulated. According to the construction method, DTBZ and MPTP are combined to construct the Parkinson's disease animal model, dosage of the MPTP is remarkably lower than that of the MPTP in a classical Parkinson's disease model induced by the MPTP, on one hand, slow progressing characteristics of the human Parkinson's diseases can be effectively simulated, on the other hand, experiment operators are obviously protected,and side effects are reduced.

Description

technical field [0001] The invention belongs to the technical field of animal model construction, and in particular relates to a method for constructing an animal model of Parkinson's disease. Background technique [0002] Parkinson's disease (PD) is a severe progressive movement disorder. In my country, the incidence rate of PD is about 1.7% among people over 65 years old, and it is the second largest neurodegenerative disease after Alzheimer's disease. Parkinson's disease is characterized pathologically by degeneration of dopaminergic neurons in the substantia nigra compacta (SNPC), loss of dopamine (DA) in the striatum, and formation of Lewy bodies by denatured aggregates of α-synuclein. It is estimated that 90% of PD patients have no family history, and sporadic parkinsonism is thought to be caused by a combination of genetic predisposition and environmental factors. [0003] Appropriate animal models help to promote the study of disease pathogenesis, and can be an eff...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/44A61K31/473A01K67/027
CPCA01K67/027A01K2267/035A61K31/44A61K31/473
Inventor 徐颖姣唐婕刘春仪赵超俞惠新陈正平谢敏浩
Owner JIANGSU INST OF NUCLEAR MEDICINE
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