帕金森病模型大鼠脑内多巴胺与铁含量的关系

Relationship between dopamine and iron contents in the brain of Parkinsonian rats

实验采用原子吸收分光光度法、快速周期伏安法、高效液相电化学检测等方法 ,研究以 6 羟基多巴( 6 OHDA)制备的帕金森病 (PD)模型大鼠黑质内铁含量的变化 ,铁对多巴胺 (DA)能神经元的直接毒性作用以及铁离子螯合剂甲磺酸去铁胺的神经保护作用。结果发现 :( 1)PD大鼠损毁侧黑质内铁含量为非标准PD大鼠的 3倍左右 ;( 2 )PD大鼠损毁侧纹状体内铁含量无明显改变 ;( 3 )单纯注射 6 OHDA的大鼠其损毁侧纹状体 (CPu)DA的释放量和含量均明显降低 ;( 4 )侧脑室预先注射甲磺酸去铁胺 ,再重复上述实验 ,损毁侧CPuDA释放量和含量均无明显改变 ;( 5 )单侧黑质内注射 4 0 μgFeCl3后 ,大鼠损毁侧CPu内DA释放量和含量显著降低。上述结果提示 ,6 OHDA可导致CPuDA释放量及含量减少 ,此过程有铁的参与。由于铁可导致DA神经元死亡 ,因此铁含量的增加可能是DA含量减少的原因之一 。

Using fast cyclic voltammetry (FCV), atomic absorption/flame emission spectrophotometry and high performance liquid chromatography for electrochemical detection, we studied the change in iron content in the substantia nigra (SN) of 6 hydroxydopamine (6 OHDA) lesioned Parkinsonian (PD) rats and the toxic effect of intranigral injection of iron on DA neurons. The neuroprotective effect of desferrioxamine mesylate was also observed. The results are as follows. (1) The iron content in SN on the lesioned side of 6 OHDA lesioned PD rats was about three times as high as that in unstandard PD rats. (2) The iron content in caudate putamen (CPu) on the lesioned side of PD rats was not different from that on the unlesioned side. (3) DA release as well as the content of DA and its metabolites were significantly decreased on the lesioned side of PD rats. (4) In the rats pretreated with intracerebroventricular desferrioxamine mesylate before 6 OHDA injection, the release and content of DA on the lesioned side were not significantly different from those on the unlesioned side. (5) Intranigral injection of 40 μg FeCl 3 resulted in a dramatic reduction of both DA release and content in CPu. The above results strongly suggest that 6 OHDA reduces the DA release from CPu, in which iron plays an important role. Elevation of iron content in SN is one of the mechanisms responsible for the reduction of DA content. Desferrioxamine mesylate may exert a protective action on dopaminergic neurons.