海洛因复吸成瘾大鼠脑NO、MDA、SOD和血脑屏障通透性的变化

发布时间：2018-07-05 02:43

本文选题：海洛因复吸成瘾 + 海洛因脱毒　；参考：《广西医科大学》2012年硕士论文

【摘要】：目的：通过模仿人类吸毒成瘾和戒毒治疗的方式,建立海洛因复吸成瘾和脱毒治疗的大鼠模型,观察大鼠一般情况和学习记忆能力的变化,及其脑组织一氧化氮、丙二醛、超氧化物歧化酶和血脑屏障通透性的变化,探讨海洛因复吸成瘾致脑损害的病理机制,为治疗提供参考依据。方法：①随机将60只成年雌性SD大鼠分为复吸组、脱毒组和对照组,每组20只。②复吸组采用吸毒成瘾→脱毒治疗→再次成瘾的方法建立海洛因复吸成瘾大鼠模型。脱毒组采用吸毒成瘾→脱毒治疗的方法建立。对照组按照复吸组的方式使用等量生理盐水。造模结束后,大鼠给予腹腔注射纳洛酮催瘾,评定成瘾强度。③证实造模成功后通过Morris水迷宫测试大鼠学习记忆能力的改变。④水迷宫测试结束后,分别从3组中随机抽取6只大鼠直接断头取脑,采用化学比色法检测大鼠额叶、顶叶、海马、尾壳核、间脑、小脑和脑干7个脑区的NO、MDA和SOD含量。⑤分别从3组大鼠中随机抽取2只大鼠通过透射电子显微镜观察大鼠脑BBB的超微结构变化。⑥分别从3组中抽取6只大鼠麻醉后经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3组中随机6只大鼠,麻醉后经股静脉给予EB,用荧光分光光度计测定脑组织EB的含量。结果：①与对照组和脱毒组大鼠相比,复吸组大鼠一般情况明显较差,纳洛酮实验阳性(p0.05)；②与脱毒组和对照组相比,复吸组大鼠逃避潜伏期延长(p0.05)；穿越平台次数减少(p0.05)；第一次穿越平台的时间延长(p0.05)；③与脱毒组和对照组比较,复吸组NO含量显著增高(p0.05),MDA含量明显增高(p0.05),SOD活性明显降低(p0.05)；④电镜观察显示,复吸组和脱毒组大鼠各脑区BBB均出现一系列通透性增高的超微结构改变；⑤与对照组和脱毒组比较,复吸组大鼠各脑区EB荧光光斑数增多(p0.05)；⑥与对照组和脱毒组比较,复吸组大鼠各脑区EB含量增多(p0.05),脱毒组比对照组EB含量增多(p0.05)。结论：①采用递增法皮下注射给药,按照成瘾-脱毒-再次成瘾的方法建立海洛因大鼠复吸模型,此建模方法稳定、有效；②海洛因复吸成瘾组大鼠的学习和记忆能力下降,脱毒组大鼠有所恢复,但低于对照组；③海洛因复吸成瘾大鼠脑NO,MDA含量增加,SOD含量下降；④海洛因复吸成瘾大鼠和另两组比,脑BBB通透性增加；⑤海洛因复吸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；⑥通过有效的脱毒治疗,海洛因复吸成瘾大鼠的学习记忆能力会恢复,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.
【学位授予单位】：广西医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R749.6

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