不同时程吗啡依赖大鼠依赖相关脑区光镜和电镜观察

目的探讨吗啡依赖中枢神经系统毒理病理不同时程的变化。方法背部皮下递增注射吗啡建立吗啡依赖大鼠模型,光镜和透射电镜下观察不同时程大鼠吗啡依赖相关脑区,即蓝斑核、中脑导水管周围灰质、黑质、豆状核、杏仁核、海马的病理组织学变化,并对突触进行计数,比较与空白对照组的差异。结果吗啡依赖大鼠6个依赖相关脑区均出现神经细胞固缩或肿胀,神经纤维肿胀,线粒体肿胀、畸形,内质网扩张,多聚核糖体解聚,突触数量增多;胶质细胞、脑膜下淋巴细胞增多,随依赖时间的延长而更加显著,并可见胶质结节形成。吗啡依赖8周组、4周组, 大鼠突触数量较空白对照组增多,其差异具有非常显著性意义(P<0．01);吗啡依赖8周组大鼠突触数量的增多,与吗啡依赖1周组、2周组大鼠比较,其差异具有非常显著性意义(P<0．01)。结论吗啡依赖大鼠依赖相关脑区神经细胞呈缺血缺氧性及退行性改变,突触数量增多,并随吗啡依赖时限的延长而明显。

Microscopic and electron microscopic observation on dependence-related cerebral regions in morphine-dependent rats

Objective To evaluate toxicopathological changes of central nervous system in rats at different morphine-dependent time. Methods Animal model of morphine-dependence in rats was established by subcutaneous injection of morphine. Histopathologic changes of coeruleus, periaqueductal gray, substantia nigra, lenticula, corpus amygdaloideun and hippocampus in morphine-dependent rats were observed by microscopy and electron microscopy, and synaptic numbers were counted and compared with those in control animals. Results Six morphine dependence-related regions in morphine-dependent groups were observed. Pyknosis or swelling of the nerve cells, swollen nerve fibers, swollen and deformed mitochondria were detected. Dilated endoplasmic reticulum and disaggregated polyribosomes were observed with increased number in synapsis. Gliocytosis and subpial infiltration of lymphocytes and monocytes became more obvious with extension of dependent time, and glial nodules were formed. Synaptic numbers were significantly increased in morphine-dependent groups at 4 or 8 weeks as compared with those in control group(P <0.01) , and morphine-dependent groups at 1 and 2 weeks (P <0. 01). Conclusion Morphine may result in ischemic-hy-poxic and degraded changes in nerve cells with increased synapses in number in dependence-related cerebral regions in rats, which reveals more evident with prolongation of dependent time.