In Vivo Imaging of the Intra- and Extracellular Redox Status in Rat Stomach with Indomethacin-Induced Gastric Ulcers Using Overhauser-Enhanced Magnetic Resonance Imaging
In Vivo Imaging of the Intra- and Extracellular Redox Status in Rat Stomach with Indomethacin-Induced Gastric Ulcers Using Overhauser-Enhanced Magnetic Resonance Imaging
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DOI：
10.1089/ars.2017.7336
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发表时间：
2018-05-09
影响因子：
6.6
通讯作者：
Utsumi, Hideo
中科院分区：
文献类型：
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作者：
Yasukawa, Keiji;Shigemi, Ryota;Utsumi, Hideo
目的：反复使用非甾体类抗炎药可诱导氧化还原状态的变化，包括活性氧（ROS）的产生，但这些变化的具体细节尚不清楚。奥弗豪斯增强磁共振成像（OMRI）已在体内用于监测几种疾病的氧化还原状态和绘制组织氧浓度。采用OMRI法监测消炎痛致胃溃疡大鼠胃细胞内和细胞外氧化还原状态，并探讨其与胃粘膜损伤的关系。结果：口服吲哚美辛（30mg /kg） 1 h后，在硝基探针给药后测定胃内OMRI。具有膜透性的硝基探针4-羟基-2,2,6,6-四甲基哌啶-1-氧（TEMPOL）的OMRI显示出氧化还原的变化，这一变化被膜透性抗氧化剂逆转。相反，用不透水探针4-三甲基铵-2,2,6,6-四甲基哌啶-1-氧（CAT-1）成像显示几乎没有氧化还原变化。通过n- 15标记的TEMPOL和n- 14标记的CAT-1的双重成像，以及另一种膜透性n- 15标记探针，3-甲氧基羰基-2,2,5,5-四甲基吡咯烷-1-氧基（MC-PROXYL）和n- 14标记的CAT-1的成像，对吲哚美辛诱导胃溃疡的活鼠胃进行氧化还原不平衡成像。MC-PROXYL预处理可抑制胃粘膜损伤，而CAT-1预处理不能抑制溃疡形成。创新点：OMRI联合双探针是一种微创成像技术，用于评估吲哚美辛治疗大鼠胃内细胞内ROS生成对胃溃疡形成的影响，这是其他方法无法做到的。结论：该方法可作为表征各种疾病发病机制的有力工具，具有一定的医学应用价值。
Aims: Repeated use of nonsteroidal anti-inflammatory drugs can induce changes in the redox status, including production of reactive oxygen species (ROS), but the specific details of these changes remain unknown. Overhauser-enhanced magnetic resonance imaging (OMRI) has been used in vivo to monitor the redox status in several diseases and map tissue oxygen concentrations. We monitored the intra- and extracellular redox status in the stomach of rats with indomethacin-induced gastric ulcers using OMRI and investigated the relationship with gastric mucosal damage.Results: One hour after oral administration of indomethacin (30 mg/kg), OMRI measurements in the stomach were made following nitroxyl probe administration. OMRI with the membrane-permeable nitroxyl probe, 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl (TEMPOL), demonstrated a redox change toward oxidation, which was reversed by a membrane-permeable antioxidant. Conversely, imaging with the impermeable probe, 4-trimethylammonium-2,2,6,6-tetramethyl-piperidine-1-oxyl (CAT-1), demonstrated little redox change. Redox imbalance imaging of a live rat stomach with indomethacin-induced gastric ulcers was produced by dual imaging of N-15-labeled TEMPOL and N-14-labeled CAT-1, in addition to imaging with another membrane-permeable N-15-labeled probe, 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl (MC-PROXYL), and N-14-labeled CAT-1. Pretreatment with MC-PROXYL suppressed gastric mucosal damage, whereas pretreatment with CAT-1 did not suppress ulcer formation.Innovation: OMRI combined with a dual probe is a less invasive imaging technique for evaluation of intracellular ROS production contributing to the formation of gastric ulcers in the stomach of indomethacin-treated rats, which cannot be done with other methods.Conclusion: This method may be a very powerful tool for characterizing the pathogenesis of various diseases and may have medical applications.