本文關(guān)鍵詞：基于“行為組學(xué)”模式焦慮動物模型評價技術(shù)體系構(gòu)建　出處：《山東中醫(yī)藥大學(xué)》2016年博士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 焦慮 動物模型 行為組學(xué) 曠場實驗 高架十字迷宮實驗 高架○迷宮實驗 明暗箱實驗 自由探索模型 三重復(fù)合裝置 新型三重復(fù)合裝置 中醫(yī)方劑

【摘要】：目的：綜述經(jīng)典焦慮動物模型評價方法,提出“行為組學(xué)”概念及其評價模式,考察經(jīng)典焦慮動物模型評價方法學(xué),構(gòu)建基于“行為組學(xué)”模式焦慮動物模型評價技術(shù)體系,用以解決當(dāng)前焦慮情緒基礎(chǔ)研究中存在諸如動物模型異質(zhì)性、重復(fù)測量效應(yīng)以及特質(zhì)與狀態(tài)焦慮動物模型相關(guān)性等科學(xué)問題。方法：首先,梳理經(jīng)典焦慮動物模型評價方法,初步提出“行為組學(xué)”概念及其評價模式；其次,考察經(jīng)典焦慮動物模型方法學(xué),包括曠場實驗(open field test,OFT)、高架十字迷宮實驗(elevated plus maze,EPM)、高架0迷宮實驗(elevated zero maze, EZM)、明暗箱實驗(light/dark box, LDB)以及自由探索模型(free exploratory paradigm,FEP)重測信度、結(jié)構(gòu)維度以及相關(guān)性等影響因素；最后,比較“行為組學(xué)”模式(Integrated vs Battery)焦慮動物模型結(jié)構(gòu)維度,并結(jié)合藥物評價,初步構(gòu)建基于“行為組學(xué)”模式焦慮動物模型評價技術(shù)體系。結(jié)果：焦慮動物模型可分為兩類：“正常“狀態(tài)”和“病理”“特質(zhì)”；“正�！薄盃顟B(tài)”焦慮動物模型又分為非條件反射和條件反射,而非條件反射焦慮動物模型又可分為探索型、社交型、防御型焦慮動物模型；其中,探索性包括OFT、EPM、EZM、 LDB、FEP,社交性主要包括社交競爭實驗,防御性包括埋藏模型和抗捕食模型；條件反射焦慮動物模型包括Geller-Seifter沖突實驗,Vogel沖突實驗,階梯實驗、四板實驗等；“病理”“特質(zhì)”焦慮動物模型又分為基因操作和特殊品系�！靶袨榻M學(xué)”(Behavioral Omics)屬于行為藥理學(xué)范疇概念,是多種動物模型的整合研究,旨在采用多種藥理學(xué)評價方法(動物模型)綜合描述實驗動物的行為譜特征；“行為組學(xué)”模式焦慮動物模型主要有Battery模式和Integrated模式,前者屬于機(jī)械組合,后者屬于有機(jī)整合。OFT穩(wěn)定參數(shù)是總得分(Total),EPM/EZM穩(wěn)定參數(shù)是開臂區(qū)進(jìn)入時間%(Otime%)和兩臂區(qū)進(jìn)入總次數(shù)(Entries),LDB穩(wěn)定參數(shù)是垂直運(yùn)動(Rear),FEP穩(wěn)定參數(shù)是陌生區(qū)垂直運(yùn)動%(Nrear%);OFT、EPM、EZM、LDB、FEP實驗參數(shù)均可分為焦慮和運(yùn)動探索兩個結(jié)構(gòu)維度；新型復(fù)合裝置(modified triple integratedapparatus,mTIA)相當(dāng)于OFT+mEZM+LDB有機(jī)整合,其包含焦慮情緒和運(yùn)動探索兩類評價參數(shù),可以具體區(qū)分抗焦慮劑(4 mg/kg地西泮可升高mTIA-mEZM-Otime%、 mTIA-LDB-Cross,而2 mg/kg阿普唑侖則無效應(yīng))以及中醫(yī)經(jīng)典方劑(8mg/kg酸棗仁湯可升高mTIA-mEZM-Otime%,8mg/kg交泰丸可升高mTIA-OFT-Ctime%)藥理效應(yīng)。結(jié)論：焦慮動物模型可分“正�！薄盃顟B(tài)”和“病理”“特質(zhì)”兩類;OFT、EPM、EZM、 LDB、FEP作為經(jīng)典焦慮動物模型應(yīng)注意性別、重復(fù)測量等影響因素及穩(wěn)定參數(shù)選��；基于“行為組學(xué)”模式焦慮動物模型評價技術(shù)體系構(gòu)建為回答焦慮動物模型基礎(chǔ)研究中存在的上述諸多問題提供可借鑒思路和方法。
[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.
【學(xué)位授予單位】：山東中醫(yī)藥大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R749.72;R-332

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