吗啡依赖和戒断大鼠脊髓内NA能神经元变化的研究

Changes of noradrenergic neurons in the spinal cord of morphine-dependence and morphine-withdrawal rat

目的探讨慢性吗啡处理及戒断后大鼠脊髓内NA能神经元的形态变化。方法24只雄性SD大鼠随机分为吗啡依赖组、吗啡戒断组和生理盐水对照组,每组8只。依赖组大鼠以腹腔注射吗啡方法建立吗啡依赖模型。戒断组大鼠在依赖模型建立后于腹腔注射纳洛酮5mg/kg诱导戒断症状,对照组大鼠注射等量生理盐水。注射24h后取脑和脊髓作冰冻切片。利用免疫组化方法检测各组大鼠脊髓及LC内NA能神经元的变化。结果正常组LC内DBH阳性细胞数为(98±17),吗啡依赖组和戒断组LC内DBH阳性细胞数分别为(212±20)和(229±27),明显高于正常组(P<0.01),但平均灰度值无明显差异。慢性吗啡处理后脊髓前角DBH阳性神经元数量增多,染色加深,后角和侧角新增加大量阳性神经元,吗啡依赖组和戒断组DBH阳性神经元增加具有极显著意义(P<0.01)。结论慢性吗啡处理和戒断引起LC和脊髓内NA能神经元增多,提示NA与吗啡依赖和戒断的形成有关,其可能是吗啡依赖及戒断的分子机制之一。

Objective To investigate the distribution, shape and number of noradrenergic neurons in the spinal cord of morphine-dependence and morphine-withdrawal rats. Methods Twenty-four male SD rats were randomly divided into three groups （n = 8 in each group）. The rats in morphine-dependence group and morphine-withdrawal group were injected intraperitoneally with morphine for 6 d till morphine dependent model was established, while the rats in control group were injected with saline. The rats in morphine-withdrawal group were injected with 5 mg/kg naloxone to induce withdrawal syndromes. In 24 h after the last injection, the brain and spinal cord were removed and cut coronally into pieces. The changes of noradrenergic neurons were measured by immunohistochemical staining. Results The number of DBH-positive neurons in LC of control group was （98 ±17）, while （212± 20） and （229± 27） respectively in morphine-dependence and morphine-with- drawal groups. More dark-stained noradrenergic neurons were found in anterior horn, while more appeared in posterior and lateral horn of spinal cord, as compared with control group. Conclusion The significant increase of noradrenergic neurons in LC and spinal cord following chronic morphine treatment and withdrawal indicates that NA was related to morphine-dependence and morphine-withdrawal syndrome, which may be involved in the molecular mechanism underlying morphine tolerance, dependence and withdrawal.