海洛因成癮大鼠腦NO、MDA、SOD和血腦屏障通透性的變化
發(fā)布時間：2019-03-01 16:46
【摘要】：目的:通過動物實(shí)驗觀察海洛因成癮大鼠腦組織一氧化氮(NO)、丙二醛(MDA)和血清超氧化物歧化酶(SOD)和血腦屏障(BBB)通透性的變化,探討海洛因成癮致腦損害的病理機(jī)制。 方法:①用隨機(jī)數(shù)字法將60只成年雌性SD大鼠分為海洛因模型組和生理鹽水對照組,每組均為30只。采用遞增法給大鼠皮下注射海洛因,人為建立海洛因成癮動物模型。對照組按同樣方法注射不含海洛因的生理鹽水。②建模結(jié)束后,大鼠腹腔注射納洛酮,按照Maldonado的戒斷癥狀評分標(biāo)準(zhǔn)判斷海洛因成癮強(qiáng)度。③通過Morris水迷宮測試2組大鼠的學(xué)習(xí)和記憶能力。④水迷宮測試結(jié)束后,分別從2組中隨機(jī)各抽取10只大鼠直接斷頭取腦,采用化學(xué)比色法檢測大鼠腦額葉皮質(zhì)、海馬、間腦、小腦和腦干5個腦區(qū)的NO、MDA和SOD含量。⑤分別從2組中隨機(jī)各抽取3只大鼠通過透射電子顯微鏡觀察大鼠BBB的超微結(jié)構(gòu)變化。⑥分別從2組中隨機(jī)各抽取7只大鼠,麻醉后經(jīng)右股靜脈給予示蹤劑伊文思藍(lán)(Evans blue ,EB),通過熒光顯微鏡觀察腦組織EB的漏出量。⑦分別從2組中隨機(jī)各抽取10只大鼠,麻醉后經(jīng)右股靜脈給予EB,用熒光分光光度計測定腦組織EB的含量。 結(jié)果:①海洛因成癮模型組大鼠體重、精神、毛色等一般情況比對照組差。②海洛因成癮模型組大鼠納洛酮試驗陽性(p0.01)。③與對照組相比,海洛因成癮模型組大鼠逃避潛伏期延長(p0.05);穿越平臺的次數(shù)減少(p0.05);第一次穿越平臺的時間延長(p0.05);平均游泳速度差別不大(p0.05)。④與對照組相比,海洛因成癮模型組大鼠腦額葉皮質(zhì)、間腦、腦干的NO含量升高(p0.05);海馬和小腦的NO含量也明顯升高(p0.01);額葉皮質(zhì)和間腦MDA的含量升高(p0.05);海馬、小腦、腦干的MDA含量明顯升高(p0.01);額葉皮質(zhì)、間腦和小腦的SOD的含量降低(p0.05);海馬和腦干的SOD含量明顯降低(p0.01)。海洛因模型組大鼠腦NO與MDA的含量呈正相關(guān)(p0.05);NO與SOD的含量呈負(fù)相關(guān)(p0.01);MDA與SOD的含量呈負(fù)相關(guān)(p0.05)。⑤電鏡觀察顯示,海洛因成癮模型組大鼠5個測試腦區(qū)BBB出現(xiàn)一系列通透性增高的超微結(jié)構(gòu)改變。⑥與對照組相比,海洛因成癮模型組大鼠5個測試腦區(qū)EB熒光光斑數(shù)增多(p0.05)。⑦與對照組相比,海洛因成癮模型組大鼠5個測試腦區(qū)EB含量升高(p0.05)。 結(jié)論:①采用遞增法皮下注射給藥建立海洛因大鼠模型,此建模方法穩(wěn)定、有效;②海洛因成癮大鼠的學(xué)習(xí)和記憶能力下降;③海洛因成癮大鼠腦NO、MDA含量增加,SOD含量下降;④海洛因成癮大鼠腦BBB通透性增加;⑤海洛因成癮腦組織出現(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(jī)制。
[Abstract]:Objective: to observe the changes of nitric oxide (NO), malondialdehyde (MDA), serum superoxide dismutase (SOD) and blood brain barrier (BBB) permeability in heroin addicted rats by animal experiment. To explore the pathological mechanism of brain damage induced by heroin addiction. Methods: 1Sixty adult female SD rats were randomly divided into two groups: heroin model group and saline control group, 30 rats in each group were divided into two groups: heroin model group (n = 30) and saline group (n = 30). An animal model of heroin addiction was established by subcutaneous injection of heroin into rats by incremental method. The control group was injected with saline without heroin in the same way. (2) after modeling, the rats were intraperitoneally injected with naloxone. The intensity of heroin addiction was evaluated according to Maldonado's score of withdrawal symptoms. 3 the learning and memory abilities of rats in two groups were tested by Morris water maze test. 4 after the water maze test, 10 rats were randomly selected from the two groups and 10 rats were directly decapitated and their brains were taken from each group. Detection of NO, in frontal cortex, hippocampus, diencephalon, cerebellum and brainstem of rats by chemical colorimetry The contents of MDA and SOD were measured by transmission electron microscope (TEM) in 3 rats of each group. 6 7 rats of each group were randomly selected from the two groups, 7 rats of each group were taken from each group, and 7 rats of each group were randomly selected to observe the ultrastructural changes of BBB of rats by transmission electron microscope. After anesthesia, the tracer Evans blue (Evans blue, EB), was given through the right femoral vein to observe the leakage of EB in the brain tissue by fluorescence microscope. 7 10 rats in each group were randomly selected from the two groups, and then EB, was given to the right femoral vein after anesthesia. The content of EB in brain tissue was determined by fluorescence spectrophotometer. Results: 1 the body weight, spirit and hair color of heroin addictive model group were worse than that of control group. 2 the naloxone test was positive in heroin addictive model group (p0.01). 3 compared with the control group, Naloxone test was positive in heroin addictive model group (p0.01). The escape latency was prolonged in heroin addiction model group (p0.05). The times of crossing the platform were decreased (p0.05) and the time of first crossing platform was prolonged (p0.05). (4) compared with the control group, the content of NO in frontal cortex, diencephalon and brainstem of heroin addicted model group increased significantly (p0.05), and the content of NO in hippocampus and cerebellum also increased significantly (p0.01). The content of MDA in frontal cortex and diencephalon increased significantly (p0.05), the content of MDA in hippocampus, cerebellum and brainstem increased significantly (p0.01), and the content of SOD in frontal cortex, diencephalon and cerebellum decreased (p0.05), and the content of SOD in frontal cortex, cerebellum and cerebellum decreased (p0.05). The content of SOD in hippocampus and brain stem decreased significantly (p0.01). There was a positive correlation between the content of NO and MDA in the brain of heroin model group (p0.05); NO was negatively correlated with the content of SOD (p0.01). There was a negative correlation between the content of MDA and SOD (p0.05). 5 the electron microscopic observation showed that a series of ultrastructural changes with increased permeability of BBB in the brain regions of the heroin addictive model group were observed. 6 compared with the control group, there were a series of ultrastructural changes in the brain BBB of the heroin addictive model group. Compared with the control group, the content of EB in the brain regions of the heroin addiction model group increased significantly (p0.05). The number of EB fluorescent spots in the brain of the heroin addictive model group was increased (p0.05) in the five test brain regions of the heroin addictive model group (p0.05). Conclusion: (1) the rat model of heroin was established by subcutaneous injection of heroin by incremental method, which was stable and effective, and the learning and memory ability of heroin addicted rats was decreased. (3) the content of NO,MDA in the brain of heroin addicted rats increased and the content of SOD decreased, and the permeability of brain BBB increased in heroin addicted rats. (5) the oxidative damage of free radical in heroin-addicted brain tissue resulted in the increase of BBB permeability, which resulted in a series of structural and functional changes in brain tissue, which may be a pathological mechanism of heroin-addicted brain injury.
【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】：2011
【分類號】：R363
本文編號：2432614
[Abstract]:Objective: to observe the changes of nitric oxide (NO), malondialdehyde (MDA), serum superoxide dismutase (SOD) and blood brain barrier (BBB) permeability in heroin addicted rats by animal experiment. To explore the pathological mechanism of brain damage induced by heroin addiction. Methods: 1Sixty adult female SD rats were randomly divided into two groups: heroin model group and saline control group, 30 rats in each group were divided into two groups: heroin model group (n = 30) and saline group (n = 30). An animal model of heroin addiction was established by subcutaneous injection of heroin into rats by incremental method. The control group was injected with saline without heroin in the same way. (2) after modeling, the rats were intraperitoneally injected with naloxone. The intensity of heroin addiction was evaluated according to Maldonado's score of withdrawal symptoms. 3 the learning and memory abilities of rats in two groups were tested by Morris water maze test. 4 after the water maze test, 10 rats were randomly selected from the two groups and 10 rats were directly decapitated and their brains were taken from each group. Detection of NO, in frontal cortex, hippocampus, diencephalon, cerebellum and brainstem of rats by chemical colorimetry The contents of MDA and SOD were measured by transmission electron microscope (TEM) in 3 rats of each group. 6 7 rats of each group were randomly selected from the two groups, 7 rats of each group were taken from each group, and 7 rats of each group were randomly selected to observe the ultrastructural changes of BBB of rats by transmission electron microscope. After anesthesia, the tracer Evans blue (Evans blue, EB), was given through the right femoral vein to observe the leakage of EB in the brain tissue by fluorescence microscope. 7 10 rats in each group were randomly selected from the two groups, and then EB, was given to the right femoral vein after anesthesia. The content of EB in brain tissue was determined by fluorescence spectrophotometer. Results: 1 the body weight, spirit and hair color of heroin addictive model group were worse than that of control group. 2 the naloxone test was positive in heroin addictive model group (p0.01). 3 compared with the control group, Naloxone test was positive in heroin addictive model group (p0.01). The escape latency was prolonged in heroin addiction model group (p0.05). The times of crossing the platform were decreased (p0.05) and the time of first crossing platform was prolonged (p0.05). (4) compared with the control group, the content of NO in frontal cortex, diencephalon and brainstem of heroin addicted model group increased significantly (p0.05), and the content of NO in hippocampus and cerebellum also increased significantly (p0.01). The content of MDA in frontal cortex and diencephalon increased significantly (p0.05), the content of MDA in hippocampus, cerebellum and brainstem increased significantly (p0.01), and the content of SOD in frontal cortex, diencephalon and cerebellum decreased (p0.05), and the content of SOD in frontal cortex, cerebellum and cerebellum decreased (p0.05). The content of SOD in hippocampus and brain stem decreased significantly (p0.01). There was a positive correlation between the content of NO and MDA in the brain of heroin model group (p0.05); NO was negatively correlated with the content of SOD (p0.01). There was a negative correlation between the content of MDA and SOD (p0.05). 5 the electron microscopic observation showed that a series of ultrastructural changes with increased permeability of BBB in the brain regions of the heroin addictive model group were observed. 6 compared with the control group, there were a series of ultrastructural changes in the brain BBB of the heroin addictive model group. Compared with the control group, the content of EB in the brain regions of the heroin addiction model group increased significantly (p0.05). The number of EB fluorescent spots in the brain of the heroin addictive model group was increased (p0.05) in the five test brain regions of the heroin addictive model group (p0.05). Conclusion: (1) the rat model of heroin was established by subcutaneous injection of heroin by incremental method, which was stable and effective, and the learning and memory ability of heroin addicted rats was decreased. (3) the content of NO,MDA in the brain of heroin addicted rats increased and the content of SOD decreased, and the permeability of brain BBB increased in heroin addicted rats. (5) the oxidative damage of free radical in heroin-addicted brain tissue resulted in the increase of BBB permeability, which resulted in a series of structural and functional changes in brain tissue, which may be a pathological mechanism of heroin-addicted brain injury.
【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】：2011
【分類號】：R363
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