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MPTP诱导小鼠黑质区铁摄取和DMT1表达增加

姜宏, 钱忠明, 谢俊霞

青岛大学医学院生理教研室,山东省神经科学研究中心. 青岛 266021；香港理工大学应用生物与化学科技学系. 香港,九龙

摘要

铁在帕金森病(Parkinson's disease,PD)的发病机制中起着非常关键的作用,为了探讨PD中铁升高的机制,本实验观察了1-甲基4-苯基-1,2,3,6-四氢吡啶(MPTP)处理小鼠黑质(substantia nigra,SN)内铁摄取及新的铁转运蛋白二价金属离子转运蛋白1(DMT1)的表达变化.结果表明:(1)MPTP处理组小鼠SN内铁染色增高,注射MPTP 7 d组明显高于3 d组.(2)MPTP处理组小鼠,酪氨酸羟化酶(TH)免疫阳性细胞数目显著减少.(3)MPTP处理组小鼠,"-IRE"型DMT1表达在各组中均增加,而"+IRE"型DMT1仅在MPTP处理后7 d才出现变化.上述结果提示,这种新发现的哺乳动物跨膜铁转运蛋白表达增加可能是引起MPTP处理小鼠SN中铁升高的关键因素,铁的升高进一步导致DA神经元的死亡。

关键词： 铁; 帕金森病; 二价金属离子转运蛋白1; 黑质

Increased DMT1 expression and iron content in MPTP-treated C57BL/6 mice

Jiang Hong, Qian Zhongming, Xie Junxia

Department of Physiology, Medical College of Qingdao University

Abstract

Iron plays a key role in Parkinson's disease (PD). To illustrate the mechanism underlyingthe increase of iron in substantia nigra (SN) in PD, changes of the expression of divalent metal transporter1 (DMT1 ) and iron content were examined in SN in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine(MPTP) treated mice using immunohistochemistry and histochemistry respectively. Following MPTP treat-ment for 3 d, elevated iron staining was found in SN. A further increase in iron content was observed after7 d. In these lesioned animals, tyrosine hydroxylase -immunoreactive DA neurons exhibited a decrease innumber and morphological changes as well. There were two isoforms of DMT1 expressed in SN of mice. Af-ter MPTP treatment, the expression of DMT1 without IRE form increased in either group, whereas DMT1with IRE form increased only after 7 d of MPTP treatment.These observations suggest that DMTl is possibly
involved in the process of iron accumulation in SN of MPTP-treated mice，which might be responsible for the subsequent death of DA neurons.

Key words: Iron;Parkinson's disease;Divalent metal transporter 1;Substantia nigra

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引用本文：

姜宏, 钱忠明, 谢俊霞. MPTP诱导小鼠黑质区铁摄取和DMT1表达增加[J]. 生理学报 2003; 55 (5): .

Jiang Hong, Qian Zhongming, Xie Junxia. Increased DMT1 expression and iron content in MPTP-treated C57BL/6 mice. Acta Physiol Sin 2003; 55 (5): (in Chinese with English abstract).