Hasaniya Nahidh W, Premaratne Shyamal, Zhang Wayne W, Razzuk Aziz, Abdul-Ghani Ayman A, Dashwood Roderick H, Eklof Bo, Tinsley Larry, McNamara J Judson
Department of Surgery, School of Medicine, Loma Linda University, Loma Linda, CA 92354, USA.
Vasc Endovascular Surg. 2011 Oct;45(7):581-91. doi: 10.1177/1538574410390715.
Acute respiratory distress syndrome (ARDS) remains a major cause of morbidity and mortality. Oxygen-free radicals (OFRs) produced during ischemia and reperfusion (IR) have been implicated as the final common pathway in the pathogenesis of this syndrome. Spin traps have been shown to decrease IR injury in several animal lung models. The hydroxylamine, OXANOH (2-ethyl-2,5,5-trimethyl-3-oxazolidine) has been proposed as an ideal spin trap that would trap extra- and intracellular OFRs producing the stable radical, OXANO• (2-ethyl-2,5,5-trimethyl-3-oxazolidinoxyl). Electron microscopy was used to investigate whether OXANOH would protect against IR injury in the rabbit lung.
OXANOH was obtained by hydrogenation of its stable radical, OXANO• using a safe laboratory technique. Several doses of OXANOH were tested to identify a nontoxic dose. Two quantitative methods were used based on the average surface area of the alveoli and average number of alveoli per unit surface area using scanning electron microscopy (SEM). A total of 20 animals were subjected to 2 hours of ischemia followed by 4 hours of reperfusion. On reperfusion, the 4 groups (N = 5) received no treatment, OXANOH, superoxide dismutase (SOD)/catalase, or oxypurinol.
A therapeutic dose of 250 μmol/L of OXANO• was suggested in this in vitro model. All the 3 treatments showed significantly less injury compared to the control group and that SOD/catalase was significantly different from OXANOH and oxypurinol (P < .008).
OXANOH ameliorated IR injury in the isolated rabbit lung, almost as effectively as SOD/catalase and oxypurinol.
急性呼吸窘迫综合征（ARDS）仍然是发病和死亡的主要原因。缺血再灌注（IR）过程中产生的氧自由基（OFRs）被认为是该综合征发病机制的最终共同途径。在几种动物肺模型中，自旋捕获剂已被证明可减少IR损伤。羟胺OXANOH（2-乙基-2,5,5-三甲基-3-恶唑烷）被认为是一种理想的自旋捕获剂，它能捕获细胞内外的OFRs，产生稳定的自由基OXANO•（2-乙基-2,5,5-三甲基-3-恶唑烷氧基）。本研究采用电子显微镜观察OXANOH是否能保护兔肺免受IR损伤。
采用安全的实验室技术，通过其稳定自由基OXANO•氢化得到OXANOH。测试了几种剂量的OXANOH以确定无毒剂量。基于肺泡平均表面积和单位表面积肺泡平均数，使用扫描电子显微镜（SEM）采用两种定量方法。总共20只动物经历2小时缺血，随后4小时再灌注。再灌注时，4组（每组n = 5）分别接受无治疗、OXANOH、超氧化物歧化酶（SOD）/过氧化氢酶或氧嘌呤醇治疗。
该体外模型提示OXANO•的治疗剂量为2,50 μmol/L。与对照组相比，所有3种治疗均显示损伤明显减轻，且SOD/过氧化氢酶与OXANOH和氧嘌呤醇有显著差异（P < 0.008）。
OXANOH改善了离体兔肺的IR损伤，效果几乎与SOD/过氧化氢酶和氧嘌呤醇相同。
