注意缺陷多动障碍模型及其病理机制研究进展

Research progress on models and pathological mechanisms of attention deficit hyperactivity disorder

总结注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)的动物模型、细胞模型,阐述其病理机制,为实验药理学研究提供理论依据。利用计算机检索中国知网、万方、PubMed等数据库有关ADHD的研究,系统总结ADHD动物模型的原理、特点及研究进展,指明其优劣;回顾ADHD细胞模型的研究现状;阐述ADHD的病理机制。ADHD动物模型可分为遗传模型(杂交鼠系模型、转基因动物模型)和非遗传模型(化学诱导模型、环境诱导模型)两大类,各种模型的表面效度、结构效度及预测效度各有侧重,应用范围也不尽相同;ADHD最常用的细胞系包括神经元细胞系和非神经元细胞系,但其研究相对不足;ADHD的发病机制主要涉及神经递质失调、神经炎症、神经能量受损。SHR是最为理想的动物模型,可以较好地模拟ADHD的症状,并对神经兴奋药物表现出良好的预测效度;SH-SY5Y细胞可表现出ADHD的多巴胺能表型,是评估细胞活力和药物安全性的重要手段;体内外研究表明神经递质失调,尤其是多巴胺缺陷假说是ADHD的核心发病机制。

To summarize the animal and cell models of attention deficit hyperactivity disorder(ADHD)and describe its pathological mechanism to provide a theoretical foundation for experimental pharmacological research.Research on ADHD was gathered from CNKI,Wanfang,PubMed,and other databases.The principles,characteristics,and research progress of ADHD animal models were comprehensively outlined,and their merits and shortcomings were highlighted.The research status of ADHD cell models was evaluated and the pathological mechanism of ADHD was explained.There are two types of animal models for ADHD:genetic models(hybrid mouse and transgenic animal models)and non⁃genetic models(chemically and environmentally induced models).The focus on face validity,construct validity,and prediction validity differs among models in addition to their application span.Neuronal and non⁃neuronal cell lines are the most often used cell lines for ADHD research,but they are understudied.The etiology of ADHD mostly involves neurotransmitter dysregulation,neuroinflammation,and decreased neuronal energy.SHR is the optimum animal model to simulate ADHD symptoms and has a strong predictive validity for neurostimulator medications.SH⁃SY5Y cells display the dopaminergic phenotype of ADHD and are a useful tool to determine cell viability and drug safety.Neurotransmitter dysregulation,particularly dopamine insufficiency,appears to be the primary pathophysiology of ADHD in accordance with in vitro and in vivo investigations.