Wong M L, Rettori V, al-Shekhlee A, Bongiorno P B, Canteros G, McCann S M, Gold P W, Licinio J
Clinical Neuroendocrinology Branch, National Institutes of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1284, USA.
Nat Med. 1996 May;2(5):581-4. doi: 10.1038/nm0596-581.
Inducible nitric oxide synthase (iNOS) is a transcriptionally regulated enzyme that synthesizes nitric oxide from L-arginine that has a key role in the pathophysiology of systemic inflammation and sepsis. Transgenic animals with a null mutation for the iNOS gene are resistant to hypotension and death caused by Escherichia coli lipopolysaccharide (LPS). The regulation of peripheral iNOS has been well studied in sepsis, but little is known about iNOS regulation in the brain during systemic inflammation or sepsis. We know that at baseline there is no detectable iNOS gene expression in the brain, but a detailed neuroanatomical study reveals that early in the course of systemic inflammation there is a profound induction of iNOS messenger RNA in vascular, glial and neuronal structures of the rat brain, accompanied by the production of nitric oxide (NO) metabolites in brain parenchyma and cerebrospinal fluid (CSF). We propose that the spillover of nitrite into the CSF has the potential to be a diagnostic marker for systemic inflammation and sepsis. Pharmacological interventions aimed at regulating iNOS function in the brain might represent a new treatment strategy in sepsis. Brain iNOS may be relevant to the pathophysiology, diagnosis and treatment of systemic inflammation and sepsis.
诱导型一氧化氮合酶（iNOS）是一种受转录调控的酶，它可将L-精氨酸合成一氧化氮，在全身炎症和脓毒症的病理生理学中起关键作用。iNOS基因发生无效突变的转基因动物对大肠杆菌脂多糖（LPS）引起的低血压和死亡具有抗性。脓毒症中外周iNOS的调控已得到充分研究，但对于全身炎症或脓毒症期间大脑中iNOS的调控却知之甚少。我们知道在基线时大脑中无法检测到iNOS基因表达，但一项详细的神经解剖学研究表明，在全身炎症过程早期，大鼠大脑的血管、神经胶质和神经元结构中iNOS信使核糖核酸会大量诱导产生，同时脑实质和脑脊液（CSF）中会产生一氧化氮（NO）代谢产物。我们认为亚硝酸盐溢出到脑脊液中有可能成为全身炎症和脓毒症的诊断标志物。旨在调节大脑中iNOS功能的药物干预可能代表脓毒症的一种新治疗策略。大脑iNOS可能与全身炎症和脓毒症的病理生理学、诊断及治疗相关。
