Cuprizone诱导的多发性硬化疾病动物模型的特点及应用

Characteristics and application of cuprizone-induced animal model of multiple sclerosis

多发性硬化(Multiple sclerosis,MS)是以人类中枢神经系统炎性脱髓鞘为主要特点的神经退行性疾病,并伴随着轴突损伤、胶质细胞增生、炎性细胞浸润等病理特征。双环己酮草酰二腙(Cuprizone,CPZ)是一种铜离子螯合剂,给小鼠饲喂CPZ可诱导小鼠中枢神经系统产生脱髓鞘病变,引起少突胶质细胞凋亡、少突胶质细胞祖细胞增殖、星形胶质细胞和小胶质细胞激活等病理变化,停止饲喂CPZ后,小鼠的中枢神经系统会逐步发生髓鞘再生现象,因此是研究MS脱髓鞘和髓鞘再生的常用模型。本文从CPZ小鼠模型构建、少突胶质细胞、星形胶质细胞、小胶质细胞以及髓鞘再生等不同方面进行了总结,并对采用CPZ模型的特色疗法进行了概括,从而为CPZ模型在科研与医学实践中的广泛应用提供了详细的理论依据。

Multiple sclerosis(MS)is a neurodegenerative disease mainly characterized by inflammatory demyelination in the central nervous system in humans,accompanied by axonal damage,gliosis,and inflammatory cell infiltration.Daily feeding with the copper chelator dicyclohexanone oxalyl dihydrazone(cuprizone,CPZ)can induce demyelination,oligodendrocyte apoptosis,proliferation of oligodendrocyte progenitor cells,and activation of astrocytes and microglia in the central nervous system in mice,while gradual remyelination occurs once CPZ is omitted from the meals.A CPZ-induced model is therefore commonly used to study demyelination and remyelination of MS.This paper focus on the construction of the CPZ mouse model,oligodendrocytes,astrocytes,microglia,and myelin regeneration,and discusses the characteristic therapies for MS in the CPZ model,to provide a theoretical basis for the wide application of this model in scientific research and medical practice.