Department of Anesthesiology, University of Virginia Health System, University of Virginia, 1 Hospital Drive, Charlottesville, VA 22908-0710, USA; Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Kangnam-Ku, Seoul, 135-710, Korea.
Neuroscience. 2010 May 5;167(2):256-60. doi: 10.1016/j.neuroscience.2010.02.017. Epub 2010 Feb 12.
Microglial cells play an important role in the inflammatory response of a broad range of brain diseases including stroke, brain infection and neurodegenerative diseases. However, there is very little information regarding how to protect microglial cells. Here, we showed that incubation of the C8-B4 mouse microglial cells with lipopolysaccharide (LPS) plus interferon-gamma (IFN gamma) induced cytotoxicity as assessed by the amount of lactate dehydrogenase (LDH) released from the cells. Preconditioning the cells with morphine for 30 min concentration-dependently reduced LPS plus IFN gamma-induced cell injury. This morphine preconditioning effect was abolished by naloxone, a general opioid receptor antagonist, by naltrindole, a selective delta opioid receptor antagonist and by 7-benzylidenenaltrexone maleate, a selective delta(1) opioid receptor antagonist. However, this protective effect was not affected by beta-funaltrexamine, a selective mu opioid receptor antagonist, nor-binaltorphimine, a selective kappa opioid receptor antagonist or naltriben, a selective delta(2) opioid receptor antagonist. LPS plus IFN gamma induced the expression of inducible nitric oxide synthase (iNOS), which was not affected by morphine preconditioning. Our results suggest that morphine induced a preconditioning effect in microglial cells. This effect may be mediated by delta 1 opioid receptors and may not be through inhibiting the expression of iNOS, a potentially harmful protein.
小胶质细胞在多种脑部疾病（包括中风、脑部感染和神经退行性疾病）的炎症反应中起着重要作用。然而，关于如何保护小胶质细胞的信息却很少。在这里，我们发现 C8-B4 小鼠小胶质细胞在脂多糖（LPS）加干扰素-γ（IFNγ）孵育下产生细胞毒性，这可通过从细胞中释放的乳酸脱氢酶（LDH）的量来评估。用吗啡预处理细胞 30 分钟可浓度依赖性地减轻 LPS 加 IFNγ引起的细胞损伤。这种吗啡预处理效应被纳洛酮、纳曲吲哚（一种选择性的δ阿片受体拮抗剂）和 7-苄基纳曲酮马来酸盐（一种选择性的 δ1阿片受体拮抗剂）所阻断，但不受β-氟纳曲胺（一种选择性的μ阿片受体拮抗剂）、 nor-binaltorphimine（一种选择性的 κ阿片受体拮抗剂）或纳曲苯（一种选择性的 δ2阿片受体拮抗剂）的影响。LPS 加 IFNγ诱导诱导型一氧化氮合酶（iNOS）的表达，而吗啡预处理对其没有影响。我们的结果表明，吗啡在小胶质细胞中诱导了一种预处理效应。这种效应可能是通过 δ1 阿片受体介导的，而不是通过抑制潜在有害蛋白 iNOS 的表达来实现的。
