基于“行为组学”模式焦虑动物模型评价技术体系构建

发布时间：2018-01-11 17:07

本文关键词：基于“行为组学”模式焦虑动物模型评价技术体系构建　出处：《山东中医药大学》2016年博士论文　论文类型：学位论文

【摘要】：目的：综述经典焦虑动物模型评价方法,提出“行为组学”概念及其评价模式,考察经典焦虑动物模型评价方法学,构建基于“行为组学”模式焦虑动物模型评价技术体系,用以解决当前焦虑情绪基础研究中存在诸如动物模型异质性、重复测量效应以及特质与状态焦虑动物模型相关性等科学问题。方法：首先,梳理经典焦虑动物模型评价方法,初步提出“行为组学”概念及其评价模式；其次,考察经典焦虑动物模型方法学,包括旷场实验(open field test,OFT)、高架十字迷宫实验(elevated plus maze,EPM)、高架0迷宫实验(elevated zero maze, EZM)、明暗箱实验(light/dark box, LDB)以及自由探索模型(free exploratory paradigm,FEP)重测信度、结构维度以及相关性等影响因素；最后,比较“行为组学”模式(Integrated vs Battery)焦虑动物模型结构维度,并结合药物评价,初步构建基于“行为组学”模式焦虑动物模型评价技术体系。结果：焦虑动物模型可分为两类：“正常“状态”和“病理”“特质”；“正常”“状态”焦虑动物模型又分为非条件反射和条件反射,而非条件反射焦虑动物模型又可分为探索型、社交型、防御型焦虑动物模型；其中,探索性包括OFT、EPM、EZM、 LDB、FEP,社交性主要包括社交竞争实验,防御性包括埋藏模型和抗捕食模型；条件反射焦虑动物模型包括Geller-Seifter冲突实验,Vogel冲突实验,阶梯实验、四板实验等；“病理”“特质”焦虑动物模型又分为基因操作和特殊品系。“行为组学”(Behavioral Omics)属于行为药理学范畴概念,是多种动物模型的整合研究,旨在采用多种药理学评价方法(动物模型)综合描述实验动物的行为谱特征；“行为组学”模式焦虑动物模型主要有Battery模式和Integrated模式,前者属于机械组合,后者属于有机整合。OFT稳定参数是总得分(Total),EPM/EZM稳定参数是开臂区进入时间%(Otime%)和两臂区进入总次数(Entries),LDB稳定参数是垂直运动(Rear),FEP稳定参数是陌生区垂直运动%(Nrear%);OFT、EPM、EZM、LDB、FEP实验参数均可分为焦虑和运动探索两个结构维度；新型复合装置(modified triple integratedapparatus,mTIA)相当于OFT+mEZM+LDB有机整合,其包含焦虑情绪和运动探索两类评价参数,可以具体区分抗焦虑剂(4 mg/kg地西泮可升高mTIA-mEZM-Otime%、 mTIA-LDB-Cross,而2 mg/kg阿普唑仑则无效应)以及中医经典方剂(8mg/kg酸枣仁汤可升高mTIA-mEZM-Otime%,8mg/kg交泰丸可升高mTIA-OFT-Ctime%)药理效应。结论：焦虑动物模型可分“正常”“状态”和“病理”“特质”两类;OFT、EPM、EZM、 LDB、FEP作为经典焦虑动物模型应注意性别、重复测量等影响因素及稳定参数选取；基于“行为组学”模式焦虑动物模型评价技术体系构建为回答焦虑动物模型基础研究中存在的上述诸多问题提供可借鉴思路和方法。
[Abstract]:Objective: to summarize the evaluation methods of classical animal models of anxiety, put forward the concept of "behavioural science" and its evaluation model, and investigate the evaluation methodology of classical animal models of anxiety. In order to solve the problem of animal model heterogeneity in the basic research of anxiety emotion, we construct an evaluation system of animal model of anxiety based on "behavioral group" model. Methods: firstly, the classical animal model evaluation method of anxiety was combed, and the concept of "behavioral group" and its evaluation model were put forward preliminarily, such as the effects of repeated measurement and the correlation between trait and state anxiety animal model. Secondly, the classical animal model of anxiety was investigated, including open field test (OFT). Elevated plus maze test and elevated zero maze test (EZM). Light / dark box (LDBs) and free exploratory models (FEPs) retest reliability. Structural dimension and correlation; Finally, the structural dimensions of the animal model of anxiety were compared in the "Behavioral Group" model (Integrated vs Battery), and combined with drug evaluation. The evaluation technique system of anxiety animal model based on "behavioral group" model was preliminarily constructed. Results: the anxiety animal model can be divided into two categories: "normal" state and "pathological" trait; The animal model of "normal" and "state" anxiety can be divided into non-conditioned reflex and conditioned reflex, and non-conditioned reflex anxiety animal model can be divided into exploratory, social and defensive anxiety animal models. Among them, exploratory includes OFTEPMEZM, LDB-FEP, social nature mainly includes social competition experiment, defensive includes burying model and anti-predation model; Conditioned reflex anxiety animal model includes Geller-Seifter conflict experiment, ladder experiment, four-board experiment and so on. The animal model of "pathology" and "trait" anxiety is divided into gene manipulation and special strain. Behavioral Omics belongs to the concept of behavioral pharmacology. It is an integrated study of many animal models, which aims at synthetically describing the behavioral spectrum characteristics of experimental animals by a variety of pharmacological evaluation methods (animal models). The anxiety animal model of "behavior group" mainly includes Battery model and Integrated model, the former belongs to mechanical combination. The latter belongs to organic integration. OFT stability parameter is total score. The stability parameter of EPM/EZM is the entry time of open arm area and the total number of times of entry of two arm area. The stability parameter of EPM/EZM is vertical motion. The stability parameter of FEP is vertical motion in strange area. The FEP parameters of OFTEPMEZM can be divided into two structural dimensions: anxiety and motor exploration. The modified triple integrated apparatus (mTIA) is equivalent to OFT mEZM LDB organic integration. It includes two kinds of evaluation parameters: anxiety and motor exploration. It can be used to distinguish that anti-anxiety agent 4 mg/kg diazepam can increase mTIA-mEZM-Otime%. MTIA-LDB-Cross. But 2 mg/kg alprazolam had no effect) and the traditional Chinese medicine prescription 8 mg / kg Zizaoren decoction could increase mTIA-mEZM-Otime%. The pharmacological effect of 8mg / kg Jietai pill was increased by mTIA-OFT-Ctime.Conclusion: the anxiety animal model can be divided into "normal" "state" and "pathological" trait. As a classical animal model of anxiety, OFTEPMEZM, LDB-FEP should pay attention to sex, repeated measurement and stability parameters. The establishment of the evaluation system of animal model of anxiety based on "behavioral group" provides some useful ideas and methods for answering the above problems in the basic research of animal model of anxiety.
【学位授予单位】：山东中医药大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R749.72;R-332

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