左旋四氢巴马汀和左旋千金藤啶碱对吗啡处理大鼠相关脑区神经胶质纤维酸性蛋白的影响

Effect of l-tetrahydropalmatine and l-stepholidine on the glial fibrillary acidic protein in the chronic morphine-treated cerebral focal regions of rats

目的:研究慢性吗啡处理大鼠相关脑区神经胶质纤维酸性蛋白(GFAP)的改变,以及左旋四氢巴马汀和左旋千金藤啶碱的干预作用。方法:以剂量递增给药方式建立吗啡慢性依赖模型后分别给予左旋四氢巴马汀、左旋千金藤啶碱和等体积蒸馏水(作为自然戒断组)治疗30 d。制备相关脑区的冰冻切片,进行GFAP的免疫组织化学染色,测定阳性细胞的平均吸收度。结果:自然戒断组大鼠前额叶皮质、伏隔核壳区、海马CA1区、黑质、杏仁核的GFAP表达与正常对照组无显著差异,但中脑腹侧背盖区(VTA)GFAP表达较正常对照组显著升高。左旋四氢巴马汀及左旋千金藤啶碱组大鼠脑VTA区GFAP表达较自然戒断组均显著降低,且可达到正常水平。结论:GFAP表达持续升高反映吗啡处理对VTA区的损伤,左旋四氢巴马汀及左旋千金藤啶碱可以使GFAP表达恢复正常,可能是它们对成瘾药物的精神依赖性有干预作用的机制之一。

Objective： To study the prophylaxis of cerebral regions of rats from morphine-induced brain injuries by l-tetrahydropalmatine and l-stepholidine. Methods： Rats were administered with an up-taper dose of morphine for 10 days and subsequently treated with distilled water, l-tetrahydropalmatine or l- stepholidine 30 mg· kg^-1 （ ig, bid） for 30 days, respectively. The rats were sacrificed under anesthesia to collect the cerebral focal tissues that were used to prepare the cerebral slices. The average density of the glial fibrillary acidic protein （GFAP） was measured with an immunocytochemical method. Results： Compared to the healthy rats, the GFAP levels in the distilled water-treated rats were normal in the cerebral focal regions including prefrontal cortex, shell of nucleus accumbens, field CA1 of hippocampus, amygdala and substantia nigra, and higher in the VTA regions of morphine-treated rats. The GFAP levels in the l-tetrahydropalmatine- or l -stepholidine-treated rats were found down to normal level. Conclusion： The morphine-treated rats experienced the impairment of VTA. The l-tetrahydropalmatine and l-stepholidine could prevent morphine-treated rats from psychological dependence by normalizing GFAP levels.