發(fā)布時間：2019-05-20 17:04

【摘要】：目的:觀察慢性束縛應(yīng)激大鼠糞樣中代謝物變化及中藥復(fù)方逍遙散的調(diào)節(jié)作用,確定與慢性束縛應(yīng)激和逍遙散作用密切相關(guān)的“代謝組學(xué)”小分子標(biāo)志化合物,以探索逍遙散對慢性心理應(yīng)激的干預(yù)作用及其機制。方法:采用每天3h連續(xù)21天束縛制動方式建立慢性應(yīng)激大鼠模型,以逍遙散為干預(yù)用藥。72只SD大鼠隨機分為正常組、模型組、逍遙散組。模型組和逍遙散組大鼠均每天給予束縛應(yīng)激,逍遙散組大鼠在束縛應(yīng)激同時每天灌服逍遙散3.854g/kg,正常組和模型組大鼠灌服0.9%生理鹽水。觀測各組大鼠的外觀、體重及攝食量等變化;采用曠場實驗和高架十字迷宮實驗觀測應(yīng)激大鼠的自主活動能力和對新異環(huán)境的探究能力;采用基于核磁共振氫譜(1H Nuclear Magnetic Resonance,1H NMR)技術(shù)的代謝組學(xué)方法檢測各組大鼠糞樣代謝譜變化,通過多元統(tǒng)計分析尋找差異性代謝產(chǎn)物,確定與慢性束縛應(yīng)激和逍遙散作用機理密切相關(guān)的“代謝組學(xué)特征”的小分子標(biāo)志化合物。結(jié)果:1外觀表現(xiàn)、體重與攝食量變化模型組大鼠的皮毛色澤等外觀表現(xiàn)較差,體重和攝食量均較正常組大鼠明顯下降(P0.05或P0.01);逍遙散干預(yù)大鼠的皮毛色澤等外觀表現(xiàn)有所改善,較模型組大鼠體重升高(P0.01),攝食量也有增加趨勢,尤其實驗第9~15天增加明顯。2行為學(xué)實驗結(jié)果2.1曠場實驗在實驗第7、21天,模型組大鼠5 min總移動路程和在中央?yún)^(qū)移動路程均較正常組減少,尤其總移動路程下降明顯(P0.05或P0.01);逍遙散干預(yù)大鼠5 min內(nèi)總移動路程和中央?yún)^(qū)移動路程均較模型組大鼠明顯增加(P0.05或P0.01)。2.2高架十字迷宮實驗在實驗第7、21天,模型組大鼠5 min內(nèi)在開放臂停留時間和進入次數(shù)均較正常大鼠減少,尤其實驗?zāi)┑?1天變化明顯(P0.05或P0.01);模型組大鼠5min內(nèi)在封閉臂停留時間增加但進入次數(shù)減少,在第21天表現(xiàn)也最明顯(P0.05或P0.01)。在實驗第21天,逍遙散干預(yù)大鼠5 min內(nèi)進入開放臂次數(shù)和在開放臂停留時間較模型組大鼠明顯增加(P0.05),而在封閉臂停留時間較單純應(yīng)激大鼠下降明顯(P0.05)但進入次數(shù)也顯著增加(P0.05)。曠場實驗和高架十字迷宮實驗說明持續(xù)21天的慢性束縛應(yīng)激引發(fā)了大鼠恐懼、焦慮、憂郁等心理反應(yīng)。3 1H NMR譜結(jié)合多元統(tǒng)計分析結(jié)果模型組和逍遙散組大鼠糞樣中Acetate、Butyrate、Glucose、Propionate、Ribose、Maltose、Valerate、Xylose 8種差異性代謝產(chǎn)物均明顯高于正常大鼠(P005或P001);逍遙散組大鼠的8種差異性代謝產(chǎn)物明顯高于模型組大鼠(P005或P001)。結(jié)論:1逍遙散對慢性心理應(yīng)激大鼠外觀表現(xiàn)、攝食量、體重具有一定的調(diào)節(jié)作用,并可緩解其恐懼、憂郁等心理反應(yīng)。2大鼠糞樣中以Glucose、Maltose、Ribose、Xylose為主的糖類和以Acetate、Butyrate、Proionate、Valerate為主的短鏈脂肪酸可作為與慢性心理應(yīng)激和逍遙散作用關(guān)系密切的差異代謝小分子標(biāo)志化合物。3調(diào)節(jié)腸道菌群種類及數(shù)量從而增加糖類及短鏈脂肪酸等小分子代謝物形成,是逍遙散干預(yù)作用的可能機制之一。
[Abstract]:Objective: To observe the changes of the metabolites in the fecal samples of the rats with chronic binding stress and the regulation of the traditional Chinese medicine, and to determine the small "metabolomics" molecular marker compounds which are closely related to the effects of the chronic binding stress and the dispersing effect. In order to explore the effect and mechanism of the intervention on the chronic psychological stress. Methods: The model of chronic stress rats was established by three-hour continuous 21-day binding braking method. The rats were randomly divided into the normal group, the model group and the scattered group in 72 SD rats. The rats of the model group and the scattered group were given the restraint stress every day, while the rats in the group of the control group and the model group were filled with the saline solution of 3.854g/ kg, and the normal group and the model group were given 0.9% normal saline. The appearance, body weight and food consumption of each group of rats were observed. The self-activity and the exploration ability of the stress rats were observed by open-field experiment and elevated cross-maze test. The nuclear magnetic resonance hydrogen spectrum (1H Nuclear Magnetic Resonance) was used. The metabolomics method of 1H NMR technique was used to detect the changes of the fecal samples in each group, and the small molecular marker compounds of the "metabolomics" which are closely related to the mechanism of chronic binding stress and the mechanism of dispersing are determined by the multivariate statistical analysis to find the difference metabolites. Results: The appearance, body weight and food consumption of rats in the model group showed poor appearance, the body weight and the food consumption decreased significantly (P0.05 or P0.01), and the appearance of the fur and the color of the rats in the rats was improved. In the model group, the weight of the rats was increased (P0.01), and the food consumption was increased, especially in the 9th to 15th day of the experiment. In particular, the total movement distance of the rats was significantly lower than that of the model group (P0.05 or P0.01), and the total movement distance and the movement distance of the central area in the rats were significantly higher than that in the model group (P0.05 or P0.01). The residence time of the open arms and the number of entering times in the model group were less than that in the normal rats (P0.05 or P0.01). The residence time of the closed arm in the model group was increased within 5 minutes, but the number of entering times decreased, and the expression in the 21st day was the most obvious (P0.05 or P0.01). In the 21st day of the experiment, the number of open arms and the number of rats in the model group with the time of the open arms increased significantly (P0.05), while the time of the closed arm was significantly lower than that of the rats with simple stress (P <0.05), but the number of access was also increased significantly (P0.05). The experimental and elevated cross-maze test showed that the chronic binding stress of 21 days resulted in the psychological reaction of the rat's fear, anxiety, and depression. The 1H NMR spectrum combined with the multivariate statistical analysis result model group and the Aetate, Buyrate, Gluconate, Propionate, Ribose, Maltaose, Valeate in the model group and the scattered group rats. The 8 difference metabolites of Xylose were significantly higher than those of normal rats (P005 or P001), and the 8 difference metabolites in the group of Xylose were significantly higher than that in the model group (P005 or P001). Conclusion:1. The effects of 1.1.1. powder on the appearance, food consumption and body weight of the rats with chronic psychological stress can be adjusted, and their fear, depression and other psychological reactions can be relieved. Valerate-based short-chain fatty acid can be used as a marker compound with small molecular marker which is closely related to the effect of chronic psychological stress and dispersion, and the type and quantity of intestinal flora can be adjusted, so as to increase the formation of small molecular metabolites such as saccharides and short-chain fatty acids, It is one of the possible mechanisms of the effect of sporadic intervention.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R285.5

【參考文獻】

相關(guān)期刊論文 前10條

1 王杰鵬;曠湘楠;張城浩;王少賢;方朝義;趙丹;申曉日;;慢性應(yīng)激肝郁脾虛模型大鼠行為學(xué)變化及逍遙散調(diào)節(jié)作用[J];河北中醫(yī)藥學(xué)報;2016年04期

2 田祖宏;聶勇戰(zhàn);;腸道微生物與腦-腸軸交互作用的研究進展[J];傳染病信息;2016年05期

3 李曉娟;馬慶宇;周巖;劉群;劉sボ，

本文編號：2481799