Objective: To study behavior capability and determine dopamine (DA) content and observe the morphological structure of neurons and astrocytes in substantia nigra (SN) of rats with chronic arsenic poisoning. Methods: The Arsenic poisoning group received arsenic (AS203) by distilled water diluted for 3 months continuously and the normal control group received equate saline. The DA content of the SN was determined by the high-performance liquid chromatography after behavior capability determined. Then, the structures of neurons and astrocytes were observed under a light microscope and quantitative analysis was performed by morphometric technique. Eventually, the ultrastructures of neurons were observed under a transmission electron microscope (TEM). Western blot was performed for detecting the expression of tyrosine hydroxylase (TH) and nitric oxide synthase (Inos) of SN in rats. Results: The behavior capability and DA content of the SN were significantly decreased in the chronic arsenic exposed group. Under the light microscope, the TH, GFAP and NSE immunopositive neurons were mainly observed in the compact part of SN. The neurons of the arsenic poisoning group ap-pearanced smaller in cell body, and karyopycnosis and Nissl bodies decreased significantly or even disappeared. Compared with the normal control group, the quantity of TH and NSE positive cells was significantly decreased in the chronic arsenic exposed groups however, astrocytes were obviously increased. Under TEM, neurons of the normal control group had regular morphology, a clear membrane, rich organelles and structural integrity; but those of the arsenic poisoning group appeared swelling, the nuclear membrane reductus, nuclear chromatin shrinkage, cytoplasmic density, mitochondria swelling, and some of organelles were transparent even into vacuolus. Compared with the normal control group, the expression of Inos in SN of the arsenic poisoning group rats was increased, while the expression of TH was significantly decreased (P< 0. 05). Conclusion: Chronic arsenic poisoning might lead to degression of both behavior capability and DA content and the pathological lesion of SN in rats, which might be one of the mechanisms of arsenic neurotoxicity.%目的:观察慢性砷中毒对大鼠行为能力及中脑黑质多巴胺含量与其形态结构的影响.方法:砷中毒组采用三氧化三砷灌胃,连续染毒3个月后观察大鼠行为能力；高效液相色谱测定中脑黑质多巴胺含量；酪氨酸羟化酶(TH)、胶质纤维酸性蛋白(GFAP)和神经元特异性烯醇化酶(NSE)免疫组织化学显色；免疫印迹法检测大鼠中脑黑质TH与iNOS蛋白的表达.结果:与正常对照组相比,砷中毒组大鼠中脑黑质多巴胺含量降低.光镜下,TH、GFAP和NSE阳性神经元主要位于黑质致密部.砷中毒组部分神经元胞体变小呈圆形或卵圆形,胞核固缩,胞质中的尼氏体减少或消失.与正常对照组相比,砷中毒组TH与NSE阳性神经元减少,而GFAP阳性神经元增多.电镜下,对照组黑质神经元形态规则,胞膜清晰,细胞器丰富,结构完整；砷中毒组神经元胞体水肿,胞质电子密度降低,细胞器减少,线粒体肿胀空泡化.与正常对照组相比,砷中毒组TH蛋白表达降低,而iNOS蛋白的表达增高.结论:慢性砷中毒可致大鼠行为能力与黑质多巴胺含量下降,TH与NSE阳性神经元减少、反应性星形胶质细胞增多,这些变化可能是砷的神经毒性作用之一.
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