大鼠海洛因中毒性脑损害的实验研究

Heroin-induced Brain Damage: An Experimental Study in Rats

目的 探讨海洛因中毒性脑损害动物模型的建立方法 ,同时研究这种脑损害的病理改变及其发病机理。材料与方法 通过建立海洛因依赖及中毒性脑损害大鼠模型 ,观察其脑部光镜与电镜改变 ,总结这种脑损害的病理变化规律。结果 成功建立海洛因依赖及中毒性脑损害大鼠模型。海洛因中毒性脑损害大鼠光镜与电镜表现 :(1)大脑皮层神经细胞变性坏死 ,累加剂量 4 336mg/kg体重组与 1931mg/kg体重组或盐水对照组之间大脑皮层神经细胞死亡数的差别有显著性意义 (P =0 .0 2 4及P =0 .0 32 ,均P <0 .0 5 ) ;(2 )海马CA1 4区光镜下主要表现神经细胞固缩坏死 ,数量减少不明显 ;(3)小脑浦肯野细胞大量固缩变性 ,部分坏死及脱失 ;(4 )首次发现海洛因中毒大鼠大脑皮质微血管周围基质溶解破坏 ;(5 )大鼠大脑及小脑髓鞘轻度变性 ,但未见典型脱髓鞘改变。结论 建立海洛因依赖及中毒动物模型可以有效地研究海洛因对中枢神经系统的毒性损害。大鼠海洛因中毒性脑损害病理改变主要是多部位神经细胞变性坏死及微血管基质的溶解破坏。

Objective To establish the animal model of heroin-induced brain damage, to investigate the pathologic changes and mechanism of such brain damage.Materials and Methods Rat model of heroin-produced toxic brain damage was established. Observation of the pathological changes of the rats' brain with both light microscope and electron microscope was carried out. The pathologic features were summarized.Results The rat models of heroin dependent and intoxication were successfully established. The pathological findings of heroin-induced brain damage were as follows. (1) The neural cells of cerebral cortex were degenerative and necrosis. Significant difference in nerve cell death existed between the 4336 mg/kg cumulative-dosage group and 1931 mg/kg cumulative-dosage group (P=0.024) or saline control group (P=0.032). (2) The main finding in the CA1-4 area of hippocampus on light microscope was pyknosis and necrosis of pyramidal cells, the decrease of pyramidal cells was not obvious. (3) Massive pyknotic degeneration, partial necrosis and loss of Purkinje's cells were found in the cerebellum. (4) Lysis and destruction of peri-microvascular stroma in the cerebral cortex was seen. (5) Mild myelinic degeneration was present in both cerebrum and cerebellum, and no typical demyelination was seen.Conclusion Rat models of heroin dependent and intoxication can be effectively used in the study of toxic damage of central nervous system caused by heroin. The main pathological features of heroin-induced brain damage are degeneration and necrosis of neural cells, and the destruction of microvascular stroma. Prolonged cerebral hypoxia due to chronic heroin abuse and direct injury of heroin may be the two main causes of cerebral impairment.