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青藤碱对吗啡依赖与戒断小鼠小脑与脊髓NO／nNOS系统的影响

刘珍, 郑济芳, 杨露青, 易岚, 胡弼

南华大学生理学教研室.湖南,衡阳 421001；南华大学遗传学教研室.湖南,衡阳 421001

摘要

该文旨在探讨青藤碱对吗啡依赖与戒断小鼠的小脑和胸腰段脊髓中一氧化氮（nitric oxide，NO）／神经元型一氧化氮合酶（neural nitric oxide synthase，nNOS）系统的影响及作用机制。采用吗啡剂量递增法建立小鼠吗啡依赖模型，用纳洛酮激发戒断症状，评价小鼠急性戒断时齿颤、扭体、直立、喷嚏、眼睑下垂等戒断症状，对成瘾小鼠用青藤碱（40mg／kg，i.P.）治疗后，再用纳洛酮激发观察戒断症状。半定量RT--PCR检测小鼠小脑和胸腰段脊髓nNOS mRNA表达变化，化学比色法和硝酸还原酶法分别测定小鼠小脑和胸腰段脊髓组织匀浆的nNOS活性与NO含量。结果显示：（1）青藤碱可以扭转由吗啡依赖引起的小鼠体重下降的趋势，减轻小鼠急性戒断时齿颤、扭体、直立、喷嚏、眼睑下垂等戒断症状；（2）青藤碱可降低小鼠吗啡依赖与戒断时在小脑与胸腰段脊髓中异常上调的nNOS mRNA水平，使酶活性下降到接近对照组水平。nNOS催化产生的NO含量与酶活性的变化一致；（3）单独使用青藤碱，小鼠没有出现类似吗啡引起的戒断症状，小脑与胸腰段脊髓中nNOS mRNA水平及酶活性没有异常升高。上述结果表明，青藤碱本身无成瘾性，但能显著减轻吗啡依赖小鼠的戒断征状，其作用机制可能与青藤碱影响小脑与脊髓中的NO／nNOS系统有关。

关键词： 青藤碱; 吗啡; 戒断; 一氧化氮合酶

Effects of sinomenine on NO/nNOS system in cerebellum and spinal cord of morphine--dependent and withdrawal mice

Liu Zhen, Zheng Jifang, Yang Luqing, Yi Lan, Hu Bi

Department of Physiology,Nanhua University.Hengyang 421001,Hunan；China

Abstract

To explore the effect of sinomenine on the nitric oxide （NO）/neural nitric oxide synthase （nNOS） system in the cerebellum and spinal cord of morphine-dependent and morphine-withdrawal Kunming mice, mice were subjected to injection of morphine with an increasing dose for 5 d, and then were treated with sinomenine （40 mg/kg, i.p.） for another 5 d. Naloxone was used to develop acute withdrawal, and the withdrawal syndromes, including teeth chattering, twisting, straightening, sneezing and ptosis, were investigated. nNOS mRNA expressions in the cerebellum and spinal cord were determined by semi-quantitative RT-PCR. nNOS activity and NO level were determined by the chemistry-colorimetry and nitrate reductase-reduction, respectively. The results obtained were as follows： （1） Sinomenine restored the decrease in body weight and alleviated the signs of morphine-withdrawal in mice. （2） Sinomenine also reduced the increases in nNOS mRNA expression and nNOS activity resulting from morphine-dependence, and simultaneously attenuated the high level of NO in both tissues following morphine-withdrawal. （3） Administration of sinomenine alone did not develop physical dependence in mice. The results obtained indicate that sinomenine may attenuate morphine addiction and significantly alleviate morphine-withdrawal symptoms, and the mechanism may be associated with the effect of sinomenine on the NO/nNOS system in the cerebellum and spinal cord.

Key words: sinomenine;Morphine;withdrawal;nitric oxide synthase

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引用本文：

刘珍, 郑济芳, 杨露青, 易岚, 胡弼. 青藤碱对吗啡依赖与戒断小鼠小脑与脊髓NO／nNOS系统的影响[J]. 生理学报 2007; 59 (3): 285-292.

Liu Zhen, Zheng Jifang, Yang Luqing, Yi Lan, Hu Bi. Effects of sinomenine on NO/nNOS system in cerebellum and spinal cord of morphine--dependent and withdrawal mice. Acta Physiol Sin 2007; 59 (3): 285-292 (in Chinese with English abstract).