In Vivo Imaging of Reactive Oxygen and Nitrogen Species in Murine Colitis
In Vivo Imaging of Reactive Oxygen and Nitrogen Species in Murine Colitis
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DOI：
10.1097/mib.0000000000000118
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发表时间：
2014-08-01
影响因子：
4.9
通讯作者：
Toivola, Diana M.
中科院分区：
文献类型：
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作者：
Asghar, M. Nadeem;Emani, Rohini;Toivola, Diana M.
背景：分析小鼠结肠炎的传统技术是侵入性的、费力的或间接的。针对特定结肠炎过程的体内成像技术的发展将有助于监测疾病进展和/或治疗效果。目的是评估化学发光探针L-012的适用性，检测活性氧和氮的物种，在体内结肠炎成像。方法：采用2只遗传性结肠炎小鼠模型；K8基因敲除（K8(-/-)）小鼠发生早期结肠炎，非肥胖糖尿病小鼠发生短暂亚临床结肠炎。采用硫酸葡聚糖钠作为化学结肠炎模型。小鼠麻醉后腹腔注射L-012，利用IVIS摄像系统对腹腔区域的化学发光信号进行成像和量化。结果：与对照组小鼠相比，K8（-/-）和非肥胖糖尿病小鼠腹部l -012介导的化学发光增加。通过组织学和髓过氧化物酶染色评估L-012信号与结肠炎表型相关。虽然与传统方法相比，L-012化学发光技术可以在更早的时间点检测到葡聚糖硫酸钠诱导的结肠炎，但小鼠间的差异很大。K8（-/-）小鼠的原位和离体L-012成像以及[F-18]FDG-PET成像证实了体内信号来源于远端结肠。L-012体内成像显示，与K8基因型无关，幼鼠体内活性氧和活性氮种类有很大差异。在衰老小鼠中，与K8（+/+）小鼠相比，K8（-/-）小鼠的L-012信号始终较高。结论：使用L-012进行体内成像是一种有用、简单、经济的工具，可以研究遗传性和可能的化学性小鼠结肠炎的水平和纵向进展。
Background: Traditional techniques analyzing mouse colitis are invasive, laborious, or indirect. Development of in vivo imaging techniques for specific colitis processes would be useful for monitoring disease progression and/or treatment effectiveness. The aim was to evaluate the applicability of the chemiluminescent probe L-012, which detects reactive oxygen and nitrogen species, for in vivo colitis imaging.Methods: Two genetic colitis mouse models were used; K8 knockout (K8(-/-)) mice, which develop early colitis and the nonobese diabetic mice, which develop a transient subclinical colitis. Dextran sulphate sodium was used as a chemical colitis model. Mice were anesthetized, injected intraperitoneally with L-012, imaged, and quantified for chemiluminescent signal in the abdominal region using an IVIS camera system.Results: K8(-/-) and nonobese diabetic mice showed increased L-012-mediated chemiluminescence from the abdominal region compared with control mice. L-012 signals correlated with the colitis phenotype assessed by histology and myeloperoxidase staining. Although L-012 chemiluminescence enabled detection of dextran sulphate sodium-induced colitis at an earlier time point compared with traditional methods, large mouse-to-mouse variations were noted. In situ and ex vivo L-012 imaging as well as [F-18]FDG-PET imaging of K8(-/-) mice confirmed that the in vivo signals originated from the distal colon. L-012 in vivo imaging showed a wide variation in reactive oxygen and nitrogen species in young mice, irrespective of K8 genotype. In aging mice L-012 signals were consistently higher in K8(-/-) as compared to K8(+/+) mice.Conclusions: In vivo imaging using L-012 is a useful, simple, and cost-effective tool to study the level and longitudinal progression of genetic and possibly chemical murine colitis.