Role of nitric oxide in inflammation-mediated neurodegeneration
Role of nitric oxide in inflammation-mediated neurodegeneration
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DOI：
10.1111/j.1749-6632.2002.tb04077.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Hong, JS
中科院分区：
文献类型：
--
作者：
Liu, B;Gao, HM;Hong, JS
越来越多的证据表明，脑部炎症与多种退行性神经系统疾病的发病密切相关，包括帕金森氏病、阿尔茨海默病、多发性硬化症、肌萎缩侧索硬化症和艾滋病痴呆。脑部炎症的标志是神经胶质细胞的激活，特别是小胶质细胞的激活，产生各种促炎和神经毒性因子，包括细胞因子、脂肪酸代谢产物、自由基--如一氧化氮(NO)和超氧化物。一氧化氮合酶诱导活化的胶质细胞产生过量的NO，被认为参与了神经退行性变。采用原代神经元-神经胶质细胞混合培养和胚胎鼠脑组织的神经胶质富集培养，系统地研究了炎症素脂多糖刺激下NO的产生与神经变性的关系。本文综述了我们在NO生成动力学、小胶质细胞和星形胶质细胞对NO积累的相对贡献、NO生成与神经退行性变之间的关系以及通过NO生成途径实现神经保护的干预要点等方面的最新研究成果。我们还描述了几种阿片类药物对小胶质细胞激活和神经保护的影响。在这些药物中，阿片受体拮抗剂纳洛酮，特别是其非阿片对映体(+)-纳洛酮有望在治疗炎症相关疾病方面具有潜在的治疗价值。
Increasing evidence has suggested that inflammation in the brain is closely associated with the pathogenesis of several degenerative neurologic disorders, including Parkinson's disease, Alzheimer's diseases, multiple sclerosis, amyotrophic lateral sclerosis, and AIDS dementia. The hallmark of brain inflammation is the activation of glial cells, especially that of microglia that produce a variety of proinflammatory and neurotoxic factors, including cytokines, fatty acid metabolites, free radicals-such as nitric oxide (NO) and superoxide. Excessive production of NO, as a consequence of nitric oxide synthase induction in activated glia, has been attributed to participate in neurodegeneration. Using primary mixed neuron-glia cultures and glia-enriched cultures prepared from embryonic rodent brain tissues, we have systemically studied the relationship between the production of NO and neurodegeneration in response to stimulation by the inflammagen lipopolysaccharide. This review summarizes our recent findings on the kinetics of NO generation, the relative contribution of microglia and astrocytes to NO accumulation, the relationship between NO, production and neurodegeneration, and points of intervention along the pathways associated with NO generation to achieve neuroprotection. We also describe our results relating to the effect of several opioid-related agents on microglial activation and neuroprotection. Among these agents, the opioid receptor antagonist naloxone, especially its non-opioid enantiomer (+)-naloxone, promises to be of potential therapeutic value for the treatment of inflammation-related diseases.