Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, USA.
Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA,; Shriners Hospital for Children, Galveston, TX, USA.
Burns. 2019 May;45(3):671-681. doi: 10.1016/j.burns.2018.10.006. Epub 2018 Oct 26.
Oxandrolone is a synthetic oral non-aromatizable testosterone derivative. This drug has been used successfully for several decades to safely treat growth delays in various diseases including Turner's syndrome. Currently the use of oxandrolone is under clinical testing in children with burn injury; the available data indicate that the anabolic steroid increases net muscle protein balance, maintains lean body mass, and reduces intensive care unit stay. Although oxandrolone is already in clinical trials in burn patients, preclinical burn-related studies with oxandrolone - especially those that go beyond muscle-related parameters and focus on burn-associated organ dysfunction, inflammatory response and wound healing - remain to be conducted. In the current project, using a well-characterized murine model of third-degree burn, we have tested the effect of oxandrolone on indices of organ injury, clinical chemistry parameters and plasma levels of inflammatory mediators. In oxandrolone-treated mice (1mg/kg/day for up to 21 days) there was a significant amelioration of burn-induced accumulation of myeloperoxidase levels in heart and lung (but not the liver and kidney) and significantly lower degree of malon dialdehyde accumulation in the liver (but not the heart, lung and kidney). Oxandrolone-treated mice showed a significant attenuation of the burn-induced elevation in circulating alkaline aminotransferase and amylase levels, while blood urea nitrogen and creatinine levels remained unaffected, indicative of protective effects of the anabolic hormone against burn-induced hepatic and pancreatic (but not renal) functional impairment. Multiple burn-induced inflammatory mediators (TNF-α, IL-1α, IL-1β, IL-4, IL-6, IL-10, IL-12, IP-10, G-CSF, GM-CSF and interferon-γ) were significantly lower in the plasma of oxandrolone-treated animals after burn injury than in the plasma of controls subjected to burns. Finally, oxandrolone significantly accelerated burn wound healing. We conclude that oxandrolone improves organ function, modulates the systemic inflammatory response and accelerates wound healing in a murine model of burn injury.
羟甲烯龙是一种合成的、非芳香化的雄性激素衍生物。这种药物已成功应用数十年，用于安全治疗包括特纳综合征在内的多种疾病引起的生长迟缓。目前，羟甲烯龙正在接受烧伤患儿的临床试验，现有数据表明，该同化类固醇可增加净肌肉蛋白平衡、维持瘦体重并减少重症监护病房的停留时间。尽管羟甲烯龙已在烧伤患者的临床试验中使用，但有关烧伤相关的羟甲烯龙的临床前研究 - 尤其是那些超越肌肉相关参数并专注于烧伤相关器官功能障碍、炎症反应和伤口愈合的研究 - 仍有待进行。在当前的项目中，我们使用一种特征明确的三度烧伤小鼠模型，检测了羟甲烯龙对器官损伤、临床化学参数和炎症介质血浆水平的影响。在羟甲烯龙治疗的小鼠（每天 1mg/kg，持续 21 天）中，烧伤引起的心脏和肺部髓过氧化物酶水平的蓄积显著改善（但肝脏和肾脏没有），肝脏丙二醛蓄积程度显著降低（但心脏、肺部和肾脏没有）。羟甲烯龙治疗的小鼠烧伤诱导的循环碱性转氨酶和淀粉酶水平升高明显减弱，而血尿素氮和肌酐水平不受影响，表明该同化激素对烧伤引起的肝和胰腺（但不是肾脏）功能损伤具有保护作用。烧伤后，羟甲烯龙治疗的动物血浆中多种烧伤诱导的炎症介质（TNF-α、IL-1α、IL-1β、IL-4、IL-6、IL-10、IL-12、IP-10、G-CSF、GM-CSF 和干扰素-γ）明显低于烧伤对照动物的血浆。最后，羟甲烯龙明显加速了烧伤伤口愈合。我们得出结论，羟甲烯龙改善了器官功能，调节了全身性炎症反应并加速了烧伤模型中的伤口愈合。
