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首页> 外文期刊>American Journal of Physiology >Neuroprotective role of delta-opioid receptors in cortical neurons.
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Neuroprotective role of delta-opioid receptors in cortical neurons.

机译：δ阿片受体在皮质神经元中的神经保护作用。

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We recently demonstrated that delta-opioid receptor (DOR) activation protects cortical neurons against glutamate-induced injury. Because glutamate is a mediator of hypoxic injury in neurons, we hypothesized that DOR is involved in neuroprotection during O2 deprivation and that its activation/inhibition may alter neuronal susceptibility to hypoxic stress. In this work, we tested the effect of opioid receptor activation and inhibition on cultured cortical neurons in hypoxia (1% O2). Cell injury was assessed by lactate dehydrogenase release, morphology-based quantification, and live/dead staining. Our results show that 1) immature neurons (days 4 and 6) were not significantly injured by hypoxia until 72 h of exposure, whereas day 8 neurons were injured after only 24-h hypoxia; 2) DOR inhibition (naltrindole) caused neuronal injury in both day 4 and day 8 normoxic cultures and further augmented hypoxic injury in these neurons; 3) DOR activation ([D-Ala2,D-Leu5]enkephalin) reduced neuronal injury in day 8 cultures after 24 h of normoxic or hypoxic exposure and attenuated naltrindole-induced injury with prolonged exposure; and 4) mu- or kappa-opioid receptor inhibition (beta-funaltrexamine or nor-binaltorphimine) had little effect on neurons in either normoxic or hypoxic conditions. Collectively, these data suggest that DOR plays a crucial role in neuroprotection in normoxic and hypoxic environments.
机译：我们最近证明，δ阿片受体（DOR）激活可保护皮质神经元免受谷氨酸诱导的损伤。因为谷氨酸是神经元缺氧损伤的介体，所以我们假设DOR在O2剥夺过程中参与神经保护，并且其激活/抑制作用可能会改变神经元对缺氧应激的敏感性。在这项工作中，我们测试了阿片受体激活和抑制对缺氧（1％O2）中培养的皮质神经元的影响。通过乳酸脱氢酶释放，基于形态学的定量和活/死染色来评估细胞损伤。我们的结果表明：1）未成熟的神经元（第4天和第6天）直到暴露72小时才受到缺氧的严重伤害，而第8天的神经元仅在缺氧24小时后受到了伤害; 2）DOR抑制（纳曲酮）在常氧培养的第4天和第8天引起神经元损伤，并进一步加重这些神经元的低氧损伤; 3）DOR激活（[D-Ala2，D-Leu5]脑啡肽）减少了常氧或低氧暴露24 h后第8天培养物中的神经元损伤，并通过长时间暴露减轻了由纳曲酮引起的损伤;和4）在常氧或低氧条件下，对μ-或κ阿片受体的抑制作用（β-氟尿嘧啶或去甲萘酚胺）对神经元的影响很小。总体而言，这些数据表明DOR在常氧和低氧环境中的神经保护中起着至关重要的作用。

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