脑电图在伽玛刀立体定向放射外科治疗猴吗啡依赖疗效评价中应用的研究
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摘要
【目的】 研究恒河猴吗啡依赖形成过程中、自然戒断后及伽玛刀立体定向放射外科(简称伽玛刀)(Stereotactic Gamma-knife Radiosurgery，GKRS)治疗后的脑电图(Electroencephalography，EEG)、脑电地形图(Brain electric activity mapping，BEAP)变化，结合戒断症状评分，利用脑电图监测变化评价脑功能变化，以判断伽玛刀治疗猴吗啡依赖的疗效。
【方法】 选取健康成年恒河猴3只，体重4～5.5公斤，随机分成2组。以剂量递增法建立恒河猴吗啡依赖动物模型。对照组(n=1，编号为猴3)，吗啡依赖后自然戒断；治疗组(n=2，编号为猴1、猴2)，吗啡依赖后自然戒断，以双侧伏膈核(Nucleus Accumbens，NAC)为靶点行伽玛刀治疗。自然戒断后及伽玛刀治疗后行戒断症状评分。给吗啡期间、伽玛刀治疗后(对照组自然戒断后)行脑电图检查，脑电图结果经二次处理得脑电地形图结果。分析对比治疗组和对照组同期脑电图的变化，脑电地形图各频带波功率值的变化。
【结果】 吗啡慢性作用后实验猴脑电图监测变化及自然戒断后戒断症状评分结果显示，3只实验猴均成功建立了吗啡依赖动物模型。吗啡依赖形成过程中，猴脑电图、脑电地形图表现α节律逐渐减弱，慢波(θ波、δ波)逐渐增加；α频带功率值逐渐下降，θ频带、δ频带功率值逐渐增加。伽玛刀治疗后，与同期对照组相比，治疗组猴脑电图、脑电地形图的异常改变明显恢复。
【结论】 脑电图监测能够从神经电生理变化方面对伽玛刀治疗猴吗啡依赖的疗效作出客观、敏感地评价。但由于样本较少，还需继续积累及研究。
[ Objective ] The purpose of this study was to study the Electroencephalography (EEG) and Brain electrical activity mapping (BEAP) changes of the Rhesus monkeys with morphine-dependence, and changes of EEG and BEAP after the treatment of the Stereotactic Gamma-knife Radiosurgery (GKRS) for the Rhesus monkeys with morphine-dependence, and to evaluate the therapeutic effects of treatment of GKRS for morphine-dependence according to changes of EEG .and BEAP.
[Methods] Three healthy aged Rhesus monkeys (Macaca mulatta) (Body weight: 4～5. 5kg ) were grouped randomly into 2 groups, the controlled group (n=1, including monkey3), in which the morphine-dependent monkey was withdrawn from morphine administration after morphine-dependence ; the treated group (n=2, including monkey1 、 monkey2), in which the morphine-dependent monkeys were treated by GKRS after morphine-dependence, the targets are bilateral nucleus accumbens (NAC) . The animal model of the Rhesus monkeys with morphine-dependence was established according to the "Dosage-increasing"
【方法】 选取健康成年恒河猴3只，体重4～5.5公斤，随机分成2组。以剂量递增法建立恒河猴吗啡依赖动物模型。对照组(n=1，编号为猴3)，吗啡依赖后自然戒断；治疗组(n=2，编号为猴1、猴2)，吗啡依赖后自然戒断，以双侧伏膈核(Nucleus Accumbens，NAC)为靶点行伽玛刀治疗。自然戒断后及伽玛刀治疗后行戒断症状评分。给吗啡期间、伽玛刀治疗后(对照组自然戒断后)行脑电图检查，脑电图结果经二次处理得脑电地形图结果。分析对比治疗组和对照组同期脑电图的变化，脑电地形图各频带波功率值的变化。
【结果】 吗啡慢性作用后实验猴脑电图监测变化及自然戒断后戒断症状评分结果显示，3只实验猴均成功建立了吗啡依赖动物模型。吗啡依赖形成过程中，猴脑电图、脑电地形图表现α节律逐渐减弱，慢波(θ波、δ波)逐渐增加；α频带功率值逐渐下降，θ频带、δ频带功率值逐渐增加。伽玛刀治疗后，与同期对照组相比，治疗组猴脑电图、脑电地形图的异常改变明显恢复。
【结论】 脑电图监测能够从神经电生理变化方面对伽玛刀治疗猴吗啡依赖的疗效作出客观、敏感地评价。但由于样本较少，还需继续积累及研究。
[ Objective ] The purpose of this study was to study the Electroencephalography (EEG) and Brain electrical activity mapping (BEAP) changes of the Rhesus monkeys with morphine-dependence, and changes of EEG and BEAP after the treatment of the Stereotactic Gamma-knife Radiosurgery (GKRS) for the Rhesus monkeys with morphine-dependence, and to evaluate the therapeutic effects of treatment of GKRS for morphine-dependence according to changes of EEG .and BEAP.
[Methods] Three healthy aged Rhesus monkeys (Macaca mulatta) (Body weight: 4～5. 5kg ) were grouped randomly into 2 groups, the controlled group (n=1, including monkey3), in which the morphine-dependent monkey was withdrawn from morphine administration after morphine-dependence ; the treated group (n=2, including monkey1 、 monkey2), in which the morphine-dependent monkeys were treated by GKRS after morphine-dependence, the targets are bilateral nucleus accumbens (NAC) . The animal model of the Rhesus monkeys with morphine-dependence was established according to the "Dosage-increasing"
引文
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[14] Ning Liu, Yancheng Liu, Yaodong Fan, et al. EEG activities in the orbitofrontal cortex and dorsolateral prefrontal cortex during the development of morphine dependence, tolerance and withdrawal in rhesus monkeys. [J]. Brain Research. 2005, 1053:137-145.
[15] MARIAELVINA SALA, MARIA PRIMULA LEONE, PAOLA LAMPUGNANI, et al. EEG power spectra and behavioral correlations in rats given chronic morphine lack of residual long-term EEG and neuronal changes. Pharmacological Research. 1995, 32, 95-103.
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[2] 邹冈主编，基础神经药理学[M]．第二版．北京：科学出版社，1999，288．
[3] Koob GF. Drug of abuse: anatomy, pharmacology and function of reward pathways. [J]. Trends Pharmacol Sci. 1992, 13: 177-184.
[4] 梁秦川，高国栋，熊华，等．伏膈核毁损对药物和应激诱导大鼠吗啡觅药行为重建的影响．[J]．立体定向和功能神经外科杂志．2003，16(4)：195-198．
[5] 贺世明，高国栋，胡三觉，等．毁损伏膈核对恒河猴吗啡觅药行为的影响．[J]．中国药物依赖性杂志．2005，14(2)：101-103．
[6] Gossop M. Relapse and survival among opiate addicts after treatment: a prospective follow up study. [J]. Br J Psychiatry. 1992, 58: 348-357.
[7] 贺世明，高国栋，王学廉，等．伏膈核毁损术治疗药物依赖性脑病术后随访一年以上的疗效分析．中国医师协会神经外科医师分会—首届全国代表大会论文汇编．上海：2005，621-624．
[8] 李冰，张金伟，刘灿虎，等．伽玛刀联合靶点戒毒5例临床初步报告．[J]．哈尔滨医科大学学报．2000，34(1)：73．
[9] 吕宁，赵春禹，张季叶等．吗啡成瘾大鼠模型建立及其伏膈核和束旁核神经元777自发放电观察．[J]．伤残医学杂志．2001，9(2)：1-3．
[10] 张树卓，李玉荣，杨宝峰，等．吗啡对新生鼠海马神经元抑制性突触后电流的作用．[J]．哈尔冰医科大学学报．2002，36(2)：97-99．
[11] Regis J, Kerkerian-Legoff L, Rey M, et al. First biochemical evidence of differential functional effects following Gamma-knife Surgery. [J]. Stereotac Funct Neurosurgery. 1996, 66: 29-38.
[12] 谭郁玲主编．临床脑电图与脑电地形图学[M]．北京：人民卫生出版社，1999，109．
[13] Itil TM. Computerized EEG: predictor of outcome in schizophrenia. [J]. Journal of Nervous and Mental Diseases. 1975, 160: 188.
[14] Mizuki, Y., Tanaka, M. Isozaki, H., et al. Periodic appearance of theta rhythm in the frontal midline area during performance of a mental task. [J]. Electroencephalogr. Clin. Neurophysiol. 1980, 49: 345-451.
[15] Khazan, N. The implication and significance of EEG, and sleep-awake activity in the study of experimental drug dependence on morphine. In: Ehrenpreis, S, Heidle, A, eds. Methods in narcotic research. New York: Marcel Dekker, 1975, 173-215.
[16] 张莉，赵妍君，张益珍，等．大鼠吗啡成瘾脑电图系统初步观察．[J]．生物医学工程学杂志．2001，18(3)：441-443．
[17] Adrian Poblano, Braulio Hernandez-Godinez, Arturo Arellano, et al. Serum Testosterone and Electroencephalography Spectra in Developmental Male Rhesus Macaca Mulatta Monkeys. [J]. Archives of Medical Research. 2004, 35: 406-410.
[18] 药物依赖性的动物实验方法(一)．[J]．中国药物依赖性杂志．1999，8(1)：23-26．
[19] Jaspers H. The ten-twenty electrodes system of the international federation. [J]. Electroencephalogr Clin Neurophysiol 1958, 10: 371-375.
[20] Nuwer M, Lehman D, Lopes da Silva, et al. IFCN guidelines for topographic and frequency analysis of EEG and EPs. Report of an IFCN committee. [J]. Electroencephalogr Clin Neurophysiol. 1994, 91:1-5.
[21] 杨文光主编．中缅树鼩、广西猕猴脑立体定位图谱[M]．昆明：云南教育出版社，1995，126-129．
[22] [日]大熊辉雄主编．周锦华<译>．临床脑电图学[M]．第五版．北京：清华大学出版社，2005，75，121．
[23] 谭郁玲主编．临床脑电图与脑电地形图学[M]．北京：人民卫生出版社，1999，108．
[24] MARIAELVINA SALA, MARIA PRIMULA LEONE, PAOLA LAMPUGNANI, et al. EEG power spectra and behavioral correlations in rats given chronic morphine lack of residual long-term EEG and neuronal changes. [J]. Pharmacological Research. 1995, 32, 95-103.
[25] ISABEL DE ANDRES, AMELIA CABALLERO. Chronic Morphine Administration in Cats: Effects on Sleep and EEG. [J]. Pharmacology Biochemistry and Behavior. 1989, 32: 519-526.
[26] Tapia-Arizmendi G, Garcia-Estrada J, Feria-Velasco A, et al. Structural changes in caudate nucleus, cerebral cortex and hippocampus induced by morphine. Light microscopy study. [J]. General Pharmacology. 1987, 18: 321-325.
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