OPIOIDS AND CELLULAR SURVIVAL

阿片类药物与细胞存活

• 批准号: 6431939
• 负责人: Tsung-Ping Ping Su
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6431939
• 关键词: endogenous opioid; heart function; heart preservation; heart transplantation; laboratory rabbit; lung; lung transplantation; myocardial ischemia /hypoxia; nonhuman therapy evaluation; perfusion; respiratory function; tissue /organ preservation

This project examines the physiological effects and the underlying biochemical mechanisms of the action of delta opioid peptide DADLE in cell survival. In this fiscal year, we found that DADLE enhances the survival of rat embryonic dopaminergic neurons in vitro and in vivo. Embryonic dopaminergic cells pretreated with DADLE promote the survival of those cells when transplanted into the 6-OHDA lesioned rats. In the methamphetamine (METH) studies, we found that administration of a single high dose of METH (25 mg/kg, i.p.) was able to cause a near complete depletion of striatal dopamine and a close to 50% loss of dopamine transporters (DAT) and tyrosine hydroxylase (TH)at the striatum. A single administration of DADLE (20 mg/kg, i.p.), given 30 min before METH, completely blocked the loss of DAT and TH, and partially blocked the depletion of dopamine caused by METH. The gene expression of a tumor necrosis factor p53 affected by METH was also blocked by DADLE. Finally, we found that DADLE can prevent the the functional loss of DAT and TH caused by METH. Thus, endogenous opioid peptide may play important role in cell survival against neurotoxicity caused by certain psychostimulants and neurotoxic agents.

该项目研究了 δ 阿片肽 DADLE 对细胞存活的生理效应和潜在的生化机制。 在本财年，我们发现 DADLE 可以增强大鼠胚胎多巴胺能神经元的体外和体内存活率。 当移植到 6-OHDA 损伤的大鼠体内时，用 DADLE 预处理的胚胎多巴胺能细胞可促进这些细胞的存活。 在甲基苯丙胺 (METH) 研究中，我们发现单次高剂量的甲基苯丙胺（25 mg/kg，腹膜内注射）能够导致纹状体多巴胺几乎完全耗尽，纹状体多巴胺转运蛋白 (DAT) 和酪氨酸羟化酶 (TH) 损失接近 50%。 在 METH 前 30 分钟给予 DADLE（20 mg/kg，腹腔注射）单次给药，完全阻断了 DAT 和 TH 的损失，并部分阻断了 METH 引起的多巴胺的消耗。 受 METH 影响的肿瘤坏死因子 p53 的基因表达也被 DADLE 阻断。 最后，我们发现DADLE可以防止METH引起的DAT和TH功能丧失。 因此，内源性阿片肽可能在对抗由某些精神兴奋剂和神经毒剂引起的神经毒性的细胞存活中发挥重要作用。