OPIOIDS AND CELLULAR SURVIVAL

该项目研究了生理效应和 δ阿片类药物作用的潜在生化机制 肽和相关蛋白质 HIT（冬眠诱导触发器） 在组织存活中。在本财年，我们发现在离体兔子中 心脏准备，其中心脏接受 18 小时的全球 缺血时，DADLE大大增强了功能恢复 心肌功能。 DADLE 的此操作被阻止 选择性 delta2 阿片受体拮抗剂。我们还延伸我们的 从 DADLE 的组织保护特性中发现 通过检查是否从周围系统到中枢神经系统 DADLE 可能可以预防甲基苯丙胺 (METH) 引起的 小鼠大脑中的多巴胺能（DA）神经元损伤。结果 表明 DADLE 剂量依赖性地阻断 METH 诱导的 DA 损坏。 DADLE 的这种作用可能涉及阿片受体 因为阿片类拮抗剂纳曲酮部分逆转了这种作用 达德尔。我们还发现 DADLE 是一种抗氧化剂 体外，表明 DADLE 的部分作用作为保护性 对抗 METH 诱导的 DA 神经元损伤的药物可能涉及 隔离已知在以下方面发挥作用的自由基 冰毒神经毒性。

This project examines the physiological effects and the underlying biochemical mechanisms of action of delta opioid peptides and a related protein HIT (Hibernation Induction Trigger) in tissue survival. In this fiscal year, we found that in isolated rabbit heart preparation in which hearts were subjected to 18 hrs of global ischemia, DADLE greatly enhances the functional recovery of myocardial functions. This action of DADLE is blocked by the selective delta2 opioid receptor antagonist. We also extend our finding on the tissue protective property of DADLE from the peripheral system to the central nervous system by examining if DADLE might protect against methamphetamine(METH)-induced dopaminergic (DA) neuronal damage in mouse brain. Results indicate that DADLE dose-dependently blocks the METH-induced DA damage. This action of DADLE may involves opioid receptors as opioid antagonist naltrexone partially reverses this action of DADLE. We also found that DADLE is an antioxidative agent in vitro, suggesting that part of the ation of DADLE as a protective agent against METH-induced DA neuronal damage may involve a sequestration of free radicals which are known to play a role in METH neurotoxicity.