魏 英,田 虹,秦 伟,陈远寿

    (遵义医学院 生理学教研室, 贵州 遵义 563099)

    基础医学研究

    外源性硫化氢对吗啡成瘾大鼠海马区cAMP信号通路和学习记忆能力的影响

    魏英,田虹,秦伟,陈远寿

    (遵义医学院 生理学教研室, 贵州 遵义563099)

    [摘要]目的 证实硫化氢能否调节吗啡成瘾大鼠海马区内腺苷酸环化酶通路，改善吗啡成瘾所导致的学习记忆相关的神经行为学影响。方法 本实验中, 应用Morris水迷宫来评估吗啡成瘾大鼠的学习记忆能力，酶联免疫试剂盒检测海马组织内腺苷酸环化酶、环磷酸腺苷及蛋白激酶A水平, 免疫印迹法检测海马内磷酸化的环磷酸腺苷反应元件结合蛋白水平。结果 Morris水迷宫测试结果表明，外源性硫化氢能提高吗啡成瘾大鼠学习记忆能力。酶联免疫及免疫印迹检测结果表明，外源性硫化氢能够明显提高吗啡成瘾大鼠海马组织内腺苷酸环化酶、环磷酸腺苷、蛋白激酶A及磷酸化的环磷酸腺苷反应元件结合蛋白水平。此外，使用胱硫醚β合成酶抑制剂盐酸羥胺的吗啡成瘾大鼠海马组织内腺苷酸环化酶、环磷酸腺苷、蛋白激酶A及磷酸化的环磷酸腺苷反应原件结合蛋白水平与吗啡组大鼠无明显差异。结论 外源性硫化氢提高吗啡成瘾大鼠海马组织内腺苷酸环化酶、环磷酸腺苷、蛋白激酶A及磷酸化的环磷酸腺苷反应元件结合蛋白水平，并改善吗啡成瘾大鼠学习记忆能力。

    [关键词]硫化氢；吗啡依赖；Morris水迷宫；cAMP信号通路；海马体；大鼠

    As a gaseous mediator and a novel type of endogenous neuron regulatory factor, H2S plays an important role in the central nervous system. It is clear that H2S can serve as a new biological gaseous transmitter that mediates a broad range of physiological processes in the nervous system.

    Opioid is known to produce analgesia via opioid receptor activation in the brain and the spinal cord. On the other hand, repeated exposure to opioids results in the development of tolerance and dependence. Opioid withdrawal syndrome, a main cause to elicit intense craving for opioids, can be observed after abrupt cessation of drug use. Of course, withdrawal syndrome can be elicited by a competitive opioid antagonist naloxone after long periods of use[1]. Chronic opioid exposure induces persistent activation of opioid receptors, which results in the supersensitivity of the adenylate cyclase (AC) signaling system[2]. Some previous studies suggest that the up-regulation of cAMP pathway is the best established mechanism involved in the development of opioid dependence and the precipitation of its withdrawal syndrome[3]. ......