TRANSMISSION DETECTOR SYSTEM FOR IN VIVO EPR STUDIES

用于体内 EPR 研究的传输检测器系统

• 批准号: 6353188
• 负责人: TADEUSZ WALCZAK
• 金额: $ 0.61万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6353188
• 关键词: Mammalia; biological products; biomaterials; biomedical resource; environmental toxicology; enzymes; hematology

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.

内毒素（革兰氏阴性细菌的脂多糖成分） 细菌）及其诱导的促炎细胞因子（白细胞介素， 肿瘤坏死因子和干扰素γ）发挥重要作用 诱导一氧化氮的产生，并参与 内毒素诱导器官起始、增殖和延伸 在主机上的损坏。 我们利用电子顺磁共振（EPR） 在这些研究中测量来自组织传播的NO的信号。 二乙基二硫代氨基甲酸盐（DETC）与亚铁同时注射 硫酸化形成疏水加合物，然后与NO络合。 所得复合物具有特征三线EPR信号。 内毒素作为推注剂量注射，并且由内毒素引起的信号被检测。 NO-Fe-（DETC）2通过将动物置于全身内进行监测 谐振器 这些数据说明了我们的EPR的灵敏度 光谱仪（运行于1. GHz）使我们能够测量 NO生产过程无创，直接从肝脏 在小鼠的诱发性幻觉发作期间。 我们能够评估 NOS抑制剂和抗炎细胞因子的作用， 白细胞介素-13对体内组织NO水平的影响。 NO水平升高 在早期（10分钟内）和晚期（6小时）时间点观察到 注射内毒素后。 IL-13处理降低了NO 在6小时可检测到80%，这意味着这可能是有价值的， 脓毒症期间的治疗方法。