海洛因成瘾大鼠脑NO、MDA、SOD和血脑屏障通透性的变化
发布时间：2019-03-01 16:46
【摘要】：目的:通过动物实验观察海洛因成瘾大鼠脑组织一氧化氮(NO)、丙二醛(MDA)和血清超氧化物歧化酶(SOD)和血脑屏障(BBB)通透性的变化,探讨海洛因成瘾致脑损害的病理机制。 方法:①用随机数字法将60只成年雌性SD大鼠分为海洛因模型组和生理盐水对照组,每组均为30只。采用递增法给大鼠皮下注射海洛因,人为建立海洛因成瘾动物模型。对照组按同样方法注射不含海洛因的生理盐水。②建模结束后,大鼠腹腔注射纳洛酮,按照Maldonado的戒断症状评分标准判断海洛因成瘾强度。③通过Morris水迷宫测试2组大鼠的学习和记忆能力。④水迷宫测试结束后,分别从2组中随机各抽取10只大鼠直接断头取脑,采用化学比色法检测大鼠脑额叶皮质、海马、间脑、小脑和脑干5个脑区的NO、MDA和SOD含量。⑤分别从2组中随机各抽取3只大鼠通过透射电子显微镜观察大鼠BBB的超微结构变化。⑥分别从2组中随机各抽取7只大鼠,麻醉后经右股静脉给予示踪剂伊文思蓝(Evans blue ,EB),通过荧光显微镜观察脑组织EB的漏出量。⑦分别从2组中随机各抽取10只大鼠,麻醉后经右股静脉给予EB,用荧光分光光度计测定脑组织EB的含量。 结果:①海洛因成瘾模型组大鼠体重、精神、毛色等一般情况比对照组差。②海洛因成瘾模型组大鼠纳洛酮试验阳性(p0.01)。③与对照组相比,海洛因成瘾模型组大鼠逃避潜伏期延长(p0.05);穿越平台的次数减少(p0.05);第一次穿越平台的时间延长(p0.05);平均游泳速度差别不大(p0.05)。④与对照组相比,海洛因成瘾模型组大鼠脑额叶皮质、间脑、脑干的NO含量升高(p0.05);海马和小脑的NO含量也明显升高(p0.01);额叶皮质和间脑MDA的含量升高(p0.05);海马、小脑、脑干的MDA含量明显升高(p0.01);额叶皮质、间脑和小脑的SOD的含量降低(p0.05);海马和脑干的SOD含量明显降低(p0.01)。海洛因模型组大鼠脑NO与MDA的含量呈正相关(p0.05);NO与SOD的含量呈负相关(p0.01);MDA与SOD的含量呈负相关(p0.05)。⑤电镜观察显示,海洛因成瘾模型组大鼠5个测试脑区BBB出现一系列通透性增高的超微结构改变。⑥与对照组相比,海洛因成瘾模型组大鼠5个测试脑区EB荧光光斑数增多(p0.05)。⑦与对照组相比,海洛因成瘾模型组大鼠5个测试脑区EB含量升高(p0.05)。 结论:①采用递增法皮下注射给药建立海洛因大鼠模型,此建模方法稳定、有效;②海洛因成瘾大鼠的学习和记忆能力下降;③海洛因成瘾大鼠脑NO、MDA含量增加,SOD含量下降;④海洛因成瘾大鼠脑BBB通透性增加;⑤海洛因成瘾脑组织出现自由基氧化损伤,造成BBB通透性增加,继而引发脑组织一系列结构及功能变化,这可能是海洛因成瘾脑损害的一个病理机制。
[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.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363
本文编号：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.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R363
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