中国研究型医院学会医学动物实验专家委员会 1中国医药生物技术协会再生医学分会 1韩发彬 1陈琳 1陈志国 1卢明 1李英俊1
作者信息
摘要
Abstract
Parkinson disease(PD)is a common neurodegenerative disease in middle-aged and elderly people.Its main clinical features include tremor at rest,bradykinesia,limb rigidity,abnormal posture and gait.In addition to motor dysfunction,most PD patients also show non-motor symptoms,including memory impairment,depression,pain,reduced olfaction,and sleep disorders.The etiology of PD has not been fully clarified,and its main pathological feature is the formation of Lewy bodies mainly composed of α-synuclein.Lewy bodies are not only present in the substantia nigra pars compacta of the midbrain,but can also spread to brain regions such as the dorsal motor nucleus of the vagus and the locus coeruleus,leading to degeneration of dopaminergic neurons.The diagnosis of PD mainly depends on clinical manifestations.Cranial CT and magnetic resonance imaging usually show no obvious abnormalities.Commonly used drugs for PD include levodopa and dopamine receptor agonists,and other therapies include deep brain stimulation and stem cell replacement therapy.Because the core pathological change in PD is the loss of midbrain-specific dopaminergic neurons,transplantation of neural stem cells or dopaminergic progenitor cells from different sources is currently the most promising therapeutic approach for PD.Before clinical application,drugs,novel instruments,and cell transplantation therapies all require preclinical studies using PD animal models to verify their efficacy and safety.Therefore,this guideline is developed under the leadership of the Committee of Experts on Medical Animal Experiments of the Chinese Research Hospital Association,in collaboration with nearly 70 experts from domestic universities,research institutes,and research-oriented hospitals,through four rounds of deliberation and three rounds of opinion solicitation and editorial revision.This guideline first reviews the etiology,clinical manifestations,and molecular mechanisms of PD,and then focuses on the commonly used PD animal models-including drug-induced(mouse,rat,and non-human primate)models and transgenic(mouse and rat)models-covering their modeling methods,mechanisms,evaluation approaches,and application scope,and summarizes the basic principles for preclinical evaluation of drug and stem cell therapies using these models.This guideline aims to provide theoretical and experimental guidance for selecting animal models in the development of new drugs and technologies for PD treatment,and to offer a reference framework for establishing standardized PD models and evaluation systems.关键词
帕金森病/帕金森病动物模型/运动障碍/多巴胺能神经元/干细胞治疗Key words
Parkinson disease/Parkinson disease animal model/Motor dysfunction/Dopaminergic neuron/Stem cell therapy分类
医药卫生
