甲基苯丙胺会加剧成年大鼠视网膜中 kainic 酸的毒性作用。

Rodrigues L G, Tavares M A, Wood J P M, Schmidt K-G, Osborne N N

Nuffield Laboratory of Ophthalmology, Oxford University, Walton Street, Oxford OX2 6AW, UK.

Neurochem Int. 2004 Dec;45(8):1133-41. doi: 10.1016/j.neuint.2004.06.011.

The recreational use of the psychoactive drug, methamphetamine has increased markedly over the last three decades. It has long been known that this drug has detrimental effects upon the mammalian brain monoaminergic system, but the long- or short-term effects on the retina, a neurological extension of the central nervous system, have received little attention. The aim of this study was, therefore, to determine whether intraocular injection of methamphetamine (MA) is toxic to the healthy adult rat retina and to analyse its effects on the compromised retina after an injection of the ionotropic glutamate receptor agonist, kainate, which is known to cause retinal neuropathology. The equivalent of 1 mM (in the vitreous humour) MA and/or kainate (40 microM) were injected intravitreally. Flash electroretinograms (ERGs) were recorded before and 2 and 4 days after treatment. Five days after treatment, animals were killed and the retinas analysed either for the immunohistochemical localisation of various antigens or for electrophoresis/Western blotting. Some animals were kept for 19 days after treatment and the retinas analysed for tyrosine hydroxylase immunoreactivity. No differences could be found between vehicle- and MA-treated retinas with respect to the nature or localisation of either tyrosine hydroxylase immunoreactivity after 5 or 19 days or other antigens after 5 days. Moreover, the normal ERG and GFAP and calretinin protein antigens were unaffected by MA. Kainate treatment, however, caused a change in the ERGs after 2 and 4 days, an alteration in every antigen localised by immunohistochemistry and an increase in the retinal levels of calretinin and GFAP proteins. Significantly, the changes seen in the b-wave amplitude and implicit time of the ERG after 4 days and the increased level of GFAP protein after 5 days following kainate treatment were enhanced when MA was co-injected. Intravitreal injection of methamphetamine had no detectable detrimental effect on the normal adult rat retina but exacerbated the damaging effects of kainic acid. Such data suggest that a neurotoxic effect of MA may be more obviously illustrated when the tissue is already compromised as occurs in, for example, ischemia.

在过去三十年中，精神活性药物甲基苯丙胺的娱乐性使用显著增加。长期以来，人们已知这种药物对哺乳动物脑单胺能系统有有害影响，但对视网膜（中枢神经系统的神经延伸部分）的长期或短期影响却很少受到关注。因此，本研究的目的是确定眼内注射甲基苯丙胺（MA）对健康成年大鼠视网膜是否有毒性，并分析其对注射离子型谷氨酸受体激动剂海藻酸后受损视网膜的影响，已知海藻酸会导致视网膜神经病理学改变。将相当于1 mM（在玻璃体液中）的MA和/或海藻酸（40 microM）玻璃体内注射。在治疗前以及治疗后2天和4天记录闪光视网膜电图（ERG）。治疗5天后，处死动物，对视网膜进行分析，以进行各种抗原的免疫组织化学定位或电泳/蛋白质印迹分析。一些动物在治疗后饲养19天，对视网膜进行酪氨酸羟化酶免疫反应性分析。在5天或19天后，就酪氨酸羟化酶免疫反应性的性质或定位而言，在注射赋形剂和MA的视网膜之间未发现差异，在5天后其他抗原方面也未发现差异。此外，正常的ERG以及胶质纤维酸性蛋白（GFAP）和钙视网膜蛋白抗原不受MA影响。然而，海藻酸治疗在2天和4天后导致ERG发生变化，通过免疫组织化学定位的每种抗原都发生改变，并且视网膜中钙视网膜蛋白和GFAP蛋白水平增加。值得注意的是，当联合注射MA时，海藻酸治疗后4天ERG的b波振幅和潜伏时间的变化以及5天后GFAP蛋白水平的增加会增强。玻璃体内注射甲基苯丙胺对正常成年大鼠视网膜没有可检测到的有害影响，但会加剧海藻酸的损伤作用。这些数据表明，当组织已经受损时，如在缺血等情况下，MA的神经毒性作用可能会更明显地表现出来。