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海洛因復(fù)吸成癮大鼠腦NO、MDA、SOD和血腦屏障通透性的變化

發(fā)布時間:2018-07-05 02:43

  本文選題:海洛因復(fù)吸成癮 + 海洛因脫毒; 參考:《廣西醫(yī)科大學(xué)》2012年碩士論文


【摘要】:目的:通過模仿人類吸毒成癮和戒毒治療的方式,建立海洛因復(fù)吸成癮和脫毒治療的大鼠模型,觀察大鼠一般情況和學(xué)習(xí)記憶能力的變化,及其腦組織一氧化氮、丙二醛、超氧化物歧化酶和血腦屏障通透性的變化,探討海洛因復(fù)吸成癮致腦損害的病理機制,為治療提供參考依據(jù)。方法:①隨機將60只成年雌性SD大鼠分為復(fù)吸組、脫毒組和對照組,每組20只。②復(fù)吸組采用吸毒成癮→脫毒治療→再次成癮的方法建立海洛因復(fù)吸成癮大鼠模型。脫毒組采用吸毒成癮→脫毒治療的方法建立。對照組按照復(fù)吸組的方式使用等量生理鹽水。造模結(jié)束后,大鼠給予腹腔注射納洛酮催癮,評定成癮強度。③證實造模成功后通過Morris水迷宮測試大鼠學(xué)習(xí)記憶能力的改變。④水迷宮測試結(jié)束后,分別從3組中隨機抽取6只大鼠直接斷頭取腦,采用化學(xué)比色法檢測大鼠額葉、頂葉、海馬、尾殼核、間腦、小腦和腦干7個腦區(qū)的NO、MDA和SOD含量。⑤分別從3組大鼠中隨機抽取2只大鼠通過透射電子顯微鏡觀察大鼠腦BBB的超微結(jié)構(gòu)變化。⑥分別從3組中抽取6只大鼠麻醉后經(jīng)股靜脈給予示蹤劑伊文思藍(Evans blue,EB),通過熒光顯微鏡觀察腦組織EB的漏出量。⑦分別從3組中隨機6只大鼠,麻醉后經(jīng)股靜脈給予EB,用熒光分光光度計測定腦組織EB的含量。結(jié)果:①與對照組和脫毒組大鼠相比,復(fù)吸組大鼠一般情況明顯較差,納洛酮實驗陽性(p0.05);②與脫毒組和對照組相比,復(fù)吸組大鼠逃避潛伏期延長(p0.05);穿越平臺次數(shù)減少(p0.05);第一次穿越平臺的時間延長(p0.05);③與脫毒組和對照組比較,復(fù)吸組NO含量顯著增高(p0.05),MDA含量明顯增高(p0.05),SOD活性明顯降低(p0.05);④電鏡觀察顯示,復(fù)吸組和脫毒組大鼠各腦區(qū)BBB均出現(xiàn)一系列通透性增高的超微結(jié)構(gòu)改變;⑤與對照組和脫毒組比較,復(fù)吸組大鼠各腦區(qū)EB熒光光斑數(shù)增多(p0.05);⑥與對照組和脫毒組比較,復(fù)吸組大鼠各腦區(qū)EB含量增多(p0.05),脫毒組比對照組EB含量增多(p0.05)。結(jié)論:①采用遞增法皮下注射給藥,按照成癮-脫毒-再次成癮的方法建立海洛因大鼠復(fù)吸模型,此建模方法穩(wěn)定、有效;②海洛因復(fù)吸成癮組大鼠的學(xué)習(xí)和記憶能力下降,脫毒組大鼠有所恢復(fù),但低于對照組;③海洛因復(fù)吸成癮大鼠腦NO,MDA含量增加,SOD含量下降;④海洛因復(fù)吸成癮大鼠和另兩組比,腦BBB通透性增加;⑤海洛因復(fù)吸成癮腦組織出現(xiàn)自由基氧化損傷,造成BBB通透性增加,繼而引發(fā)腦組織一系列結(jié)構(gòu)及功能變化,這可能是海洛因成癮腦損害的一個病理機制;⑥通過有效的脫毒治療,海洛因復(fù)吸成癮大鼠的學(xué)習(xí)記憶能力會恢復(fù),氧自由基的清除力提高。
[Abstract]:Objective: to establish a rat model of heroin relapse addiction and detoxification by imitating the way of drug addiction and detoxification treatment, and to observe the changes of general situation, learning and memory ability, nitric oxide and malondialdehyde (MDA) in brain tissue of rats. The changes of superoxide dismutase (SOD) and blood-brain barrier permeability (BBB) were used to explore the pathological mechanism of brain damage caused by heroin relapse addiction. Methods 60 adult female Sprague-Dawley rats were randomly divided into relapse group, detoxification group and control group. The detoxification group was established by drug addiction and detoxification therapy. The control group was treated with the same amount of saline as the relapse group. After the model was finished, the rats were given intraperitoneal injection of naloxone to induce addiction, and the intensity of addiction was assessed. 3. After testing the learning and memory ability of rats by Morris water maze, the learning and memory ability of rats was tested by Morris water maze after the completion of the water maze test. Six rats were randomly selected from 3 groups to take out their brains. The frontal lobe, parietal lobe, hippocampus, caudate putamen nucleus and diencephalon were detected by chemical colorimetry. Contents of MDA and SOD in cerebellum and brainstem in 7 brain regions, 2 rats were randomly selected from 3 groups to observe the ultrastructural changes of BBB in the brain by transmission electron microscope. 6 rats were drawn from 3 groups respectively to study the ultrastructural changes of BBB in the brain. 6 rats were drawn from 3 groups. After intoxicated rats were given the tracer Evans blue EB through femoral vein. The brain tissue leakage volume of EB was observed by fluorescence microscope, and 6 rats were randomly divided into three groups. After anesthesia, EB2 was given via femoral vein, and the content of EB in brain tissue was measured by fluorescence spectrophotometer. Results compared with the control group and the detoxified group, the general condition of the rats in the relapse group was significantly worse than that in the control group. The naloxone test positive (p0.05) naloxone test showed that the escape latency was prolonged (p0.05), the number of crossing the platform was decreased (p0.05) in the relapse group compared with that in the control group and the control group. Compared with the control group and the detoxified group, the no content in the relapse group was significantly increased (p0.05) MDA content was significantly increased (p0.05) SOD activity was significantly decreased (p0.05). There were a series of ultrastructural changes in BBB of rats in the relapse group and the detoxification group. Compared with the control group and the detoxification group, the number of EB fluorescence spots (p0.05) in each brain area of the relapse group was higher than that in the control group and the detoxification group, and compared with the control group and the detoxification group. The content of EB in brain regions of rats in relapse group was higher than that in control group (p0.05), and that in virus-free group was higher than that in control group (p0.05). Conclusion the model of heroin relapse in rats was established according to the method of addiction, detoxification and re-addiction. The model was stable, and the learning and memory ability of rats in the effective heroin relapse addiction group was decreased. Compared with the other two groups, the brain BBB permeability was increased in the detoxified rats, but lower than that in the control group (P < 0.05), but the content of MDA in the brain of the rats with heroin relapse addiction was higher than that in the control group. The content of SOD in the brain of rats with heroin relapse addiction was lower than that in the other two groups. (5) oxidative damage of free radical appeared in brain tissue of heroin relapse addiction, which resulted in the increase of BBB permeability and a series of structural and functional changes of brain tissue, which may be a pathological mechanism of brain damage in heroin addiction; 6 through effective detoxification treatment, the learning and memory ability of heroin relapse addiction rats will recover, and the scavenging ability of oxygen free radicals will be improved.
【學(xué)位授予單位】:廣西醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2012
【分類號】:R749.6

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