TRANSMISSION DETECTOR SYSTEM FOR IN VIVO EPR STUDIES

内毒素(革兰氏阴性菌的内毒素成分 细菌)及其诱导的促炎细胞因子(白细胞介素类， 肿瘤坏死因子和干扰素-γ)发挥着重要作用 诱导一氧化氮的产生，并参与 内毒素诱导器官的起始、增殖和延伸 主机损坏。我们利用电子顺磁共振(EPR) 在这些研究中，测量来自组织中携带NO的信号。 二乙基二硫代氨基甲酸酯(DETC)与亚铁同时注射 硫酸盐形成疏水加合物，然后与NO络合。 得到的复合体具有特征的三线EPR信号。 内毒素作为推注剂量注射，信号产生于 通过将动物放入全身来监测NO-Fe-(DETC)2 谐振器。这些数据说明了我们的EPR的敏感性 光谱仪(工作在1 GHz)使我们能够测量时间 NO的产生过程是无创的，直接从肝脏产生 在小鼠的一次诱发的幻觉发作中。我们能够评估 一氧化氮合酶抑制剂和抗炎细胞因子的作用， IL-13对体内组织NO水平的影响。NO水平升高 在早(10分钟内)和晚(6小时)时间点观察到 在注射内毒素后。IL-13治疗可降低NO含量。 在6小时内可检测到80%，这意味着这可能是有价值的 脓毒症期间的治疗方法。

Endotoxin (the lipopolysaccharide component of Gram-negative bacteria) and the pro-inflamatory cytokines it induces (interleukins, tumor necrosis factor, and interferon gamma) play and important role in inducing nitric oxide production, and participate in the initiation, propagation and extension of endotoxin-induced organ damage in the host. We utilized Electron Paramagnetic Resonance (EPR) in these studies to measure the signal from tissue borne NO. Diethyldithiocarbamate (DETC) was injected simultaneously with ferrous sulfate to from a hydrophobic adduct which then complexed with NO. The resulting complex has a characteristic three-line EPR signal. Endotoxin was injected as a bolus dose, and the signal arising from NO-Fe-(DETC)2 monitored by placing the animal inside a whole body resonator. The data illustrate how the sensitivity of our EPR spectrometer (operating at 1. GHz) enabled us to measure the time course of NO production non-invasively, and directly from the liver during an induced spectic episode in mice. We were able to assess the effects of inhibitors of NOS, and the anti-inflammatory cytokine, Interleukin-13, on tissue NO levels in vivo. Increased levels of NO were observed at early (within 10 min) and late (at 6 hrs) time points following endotoxin injection. IL-13 treatment reduced the NO detectable at 6 hrs by 80%, and implies that this may be valuable as a means of therapy during sepsis.