基于中西医临床病症特点的难治性癫痫动物模型评价与分析

Evaluation and Analysis of Animal Models of Refractory Epilepsy Reflecting Clinical Characteristics of Traditional Chinese and Western Medicine

目的基于难治性癫痫的中西医临床病症特点,对比评估现有难治性癫痫动物模型,评价模型的有效性和局限性,并探讨整合中西医理论、优化模型构建的思路,为难治性癫痫的机制阐明和防治提供新的研究方向。方法通过查阅相关文献,整理分析相关资料,总结现有难治性癫痫动物模型复制方法、动物品系和模型优缺点,以难治性癫痫的西医诊断标准与中医辨证标准为依据,对现有的动物模型与临床症状的吻合度进行分析和评价。结果总结现有的难治性癫痫动物模型,发现电点燃和化学点燃是目前常用的造模方法,锂-匹罗卡品模型和海马内海人酸模型与中西医临床病症特点吻合度较高,是目前应用较广泛的动物模型。现有模型多侧重于模拟难治性癫痫的病理改变,而对于中医学所重视的先天禀赋、情志失调等因素考虑不足,因此在模拟难治性癫痫的病因复杂性、临床异质性和药物治疗反应性等方面仍存在一定局限。结论复制动物模型虽然可以在一定程度上反映其发病机制,但与机体的自然发病状态和临床表现仍然有较大差异。现有难治性癫痫动物模型多采用电刺激或化学药物诱导,在模拟癫痫持续状态、耐药性方面有一定优势,但仍存在诱导方法单一、病理改变不够复杂等局限。未来可尝试整合中医辨证分型与常规的电刺激或化学药物诱导方法,通过模拟多种致病因素,建立涵盖不同中医证型的难治性癫痫动物模型。同时,采用行为学、电生理、影像学和组织病理学等多维度指标,构建更全面的评价体系,以提高模型的临床相关性和转化应用价值。在造模过程中,可通过夹尾法、慢性束缚法、颈部带枷单笼喂养法等方式建立肝郁证模型;采用高脂饲料喂饲法建立痰凝证模型;使用夹尾+肾上腺素注射的方法建立气滞血瘀证模型;应用惊恐伤肾结合劳倦游泳建立肾虚精亏证模型等。还可通过改变光照和温度条件,模拟环境中的阴阳变化,研究环境变化对中医动物模型的影响。为难治性癫痫的治疗与研究提供更多思路。

Objective Based on the clinical characteristics of refractory epilepsy in traditional Chinese and Western medicine,this study compares the existing animal models of refractory epilepsy,evaluates the effectiveness and limitations of the models,and explores the integration of traditional Chinese and Western medicine theory and optimization of model construction.Our aim is to provide new research directions for elucidating the mechanism and prevention of refractory epilepsy.Methods By reviewing relevant literature and summarizing the available data,we examined current refractory epilepsy animal models,focusing on their replication methods,animal strains,as wellas advantages and disadvantages of animal models.Based on the Western medicine diagnostic criteria and traditional Chinese medicine syndrome differentiation criteria for refractory epilepsy,the coincidence of existing animal models and clinical symptoms were analyzed and evaluated.Results Our review of existing refractory epilepsy animal models revealed that electrical and chemical kindling are common modeling methods.The lithium-pilocarpine model and the intrahippocampal kainic acid model show high congruence with the symptom characteristics of traditional Chinese and Western medical clinical diagnosis and are widely used.Existing models mostly focus on simulating the pathological changes of refractory epilepsy,while neglecting the factors such as congenital endowment and emotional disorders,which have been emphasized in traditional Chinese medicine.Therefore,there are still certain limitations in simulating the complexity of etiology,clinical heterogeneity,and drug treatment responsiveness of refractory epilepsy.Conclusion Although replicating animal models can reflect their pathogenesis to some extent,there are still significant differences between them and the natural pathological state and clinical manifestations of the body.The existing animal models of refractory epilepsy mostly use electrical stimulation or chemical drug induction,which has certain advantages in simulating epileptic persistence and drug resistance.However,there are still limitations such as a single induction method and insufficiently complex pathological changes.In the future,efforts can be made to integrate traditional Chinese medicine syndrome differentiation and conventional electrical stimulation or chemical drug induction methods.By simulating multiple pathogenic factors,a refractory epilepsy animal model covering different traditional Chinese medicine syndrome types can be established.At the same time,multi-dimensional indicators such as behavior,electrophysiology,imaging,and histopathology can be used to construct a more comprehensive evaluation system,in order to improve the clinical relevance and translational application value of the model.During the modeling process,liver depression syndrome models can be established through methods such as tail clamping,chronic restraint,and single cage feeding with neck shackle.A model of phlegm coagulation syndrome can be established using high-fat feed feeding method.A model of qi stagnation and blood stasis syndrome can be established using tail clip and adrenaline injection.A model of essence exhaustio due to kidney deficiency syndrome can be established by combining panic induced kidney injury with fatigue swimming.It is also possible to simulate changes of yin-yang in the environment by altering lighting and temperature conditions and study the impact of environmental changes on traditional Chinese medicine animal models.The aim of this study is to provide more ideas for the treatment and research of refractory epilepsy.