急、慢性铁负载大鼠黑质内铁及TH样阳性细胞变化的相伴关系

许多研究证实Parkinson病(PD)患者黑质内铁含量显著增高,并伴有铁代谢的改变,由于铁的细胞毒作用和它能够促进羟自由基产生的能力,使其在PD中的作用不容忽视。本实验用葡聚糖铁建立急慢性铁负载模型大鼠,采用酪氨酸羟化酶(TH)免疫组织化学技术和Perls铁染色技术分别观察了黑质中多巴胺能神经元的存活情况以及黑质中铁含量的变化。结果显示:(1)急性铁负载模型组:黑质中TH阳性细胞数明显减少,而铁染色阳性细胞数明显增多,与正常对照组相比差异有高度显著性(P<0.05);(2)慢性铁负载模型组:黑质中TH阳性细胞数明显减少,铁染色阳性细胞数则明显增多,与正常对照组相比差异有高度显著性(P<0.05);(3)慢性组与急性组相比,黑质内TH阳性细胞数的减少和铁染色阳性细胞数的增多更为明显,差异有高度显著性(P<0.05)。上述结果提示,葡聚糖铁铁负载模型可引起黑质内铁增多,过量铁可导致黑质内多巴胺能神经元变性死亡,慢性铁负载对多巴胺能神经元的损伤作用大于急性铁负载损伤。

CONCOMITANT RELATIONSHIP OF IRON AND TH-POSITIVE NEURONS IN THE SUBSTANTIA NIGRA OF ACUTE AND CHRONIC IRON-OVERLOADED RATS

Previous studies have indicated that iron level increased in the substantia nigra (SN) of Parkinson's disease(PD) patients and iron metabolism was also changed in these patients. Due to its toxicity and ability to catalyze the formation of hydroxyl free radicals, the role of iron in PD can not be ignored. In the present study, the acute and chronic iron-overloaded rats were made by iron dextran. Tyrosine hydroxylase (TH) immunohistochemistry was employed to measure TH-like immunoreactive (TH-ir) neurons in SN. on the other hand, iron level in the SN was also measured by Perls' iron staining. The results were as follows; (1)In the group of acute iron-overloaded rats, TH-ir neurons in the SN significantly decreased, however, an apparent increase in iron staining was found (P<0. 05) ; (2)In the group of chronic iron-overloaded rats, TH-ir neurons in the SN also decreased, while the number of neurons of the iron staining increased (P<0. 05) ; (3)Compared with these two groups, the decrease of TH-ir neurons and increase of iron staining neurons were more apparent in chronic group than that in acute group (P< 0. 05). The above results suggest that iron dextran overload can increase the iron amount and excessive iron can cause the degeneration and death of dopaminergic neurons in the SN. The damage of the chronic iron overload to dopaminergic neurons is stronger than the acute iron overload.