Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, 233 South 10th. Street BLSB 306, Philadelphia, PA, 19107, USA.
J Cachexia Sarcopenia Muscle. 2012 Sep;3(3):199-211. doi: 10.1007/s13539-012-0062-x. Epub 2012 Mar 29.
Burn injury results in a chronic inflammatory, hypermetabolic, and hypercatabolic state persisting long after initial injury and wound healing. Burn survivors experience a profound and prolonged loss of lean body mass, fat mass, and bone mineral density, associated with significant morbidity and reduced quality of life. Understanding the mechanisms responsible is essential for developing therapies. A complete characterization of the pathophysiology of burn cachexia in a reproducible mouse model was lacking.
Young adult (12-16 weeks of age) male C57BL/6J mice were given full thickness burns using heated brass plates or sham injury. Food and water intake, organ and muscle weights, and muscle fiber diameters were measured. Body composition was determined by Piximus. Plasma analyte levels were determined by bead array assay.
Survival and weight loss were dependent upon burn size. The body weight nadir in burned mice was 14 days, at which time we observed reductions in total body mass, lean carcass mass, individual muscle weights, and muscle fiber cross-sectional area. Muscle loss was associated with increased expression of the muscle ubiquitin ligase, MuRF1. Burned mice also exhibited reduced fat mass and bone mineral density, concomitant with increased liver, spleen, and heart mass. Recovery of initial body weight occurred at 35 days; however, burned mice exhibited hyperphagia and polydipsia out to 80 days. Burned mice had significant increases in serum cytokine, chemokine, and acute phase proteins, consistent with findings in human burn subjects.
This study describes a mouse model that largely mimics human pathophysiology following severe burn injury. These baseline data provide a framework for mouse-based pharmacological and genetic investigation of burn-injury-associated cachexia.
烧伤会导致慢性炎症、代谢亢进和分解代谢亢进，在初始损伤和伤口愈合后仍会持续很长时间。烧伤幸存者会经历明显且持久的去脂体重、脂肪量和骨矿物质密度的损失，伴随显著的发病率和生活质量下降。了解相关机制对于开发治疗方法至关重要。在可重现的小鼠模型中，烧伤恶病质的病理生理学仍缺乏全面的特征描述。
采用加热的黄铜板对年轻成年（12-16 周龄）雄性 C57BL/6J 小鼠进行全层烧伤或假伤。测量食物和水的摄入量、器官和肌肉重量以及肌纤维直径。通过 Piximus 测定身体成分。通过珠阵列测定法测定血浆分析物水平。
存活率和体重减轻取决于烧伤面积。烧伤小鼠的体重最低点在 14 天，此时我们观察到总体重、瘦体组织质量、单个肌肉重量和肌纤维横截面积减少。肌肉损失与肌肉泛素连接酶 MuRF1 的表达增加有关。烧伤小鼠还表现出脂肪量和骨矿物质密度降低，同时肝、脾和心脏重量增加。在 35 天时恢复初始体重；然而，烧伤小鼠在 80 天时仍表现出多食和多饮。烧伤小鼠的血清细胞因子、趋化因子和急性期蛋白显著增加，与人类烧伤患者的发现一致。
本研究描述了一种小鼠模型，该模型在很大程度上模拟了严重烧伤后的人类病理生理学。这些基线数据为基于小鼠的烧伤相关性恶病质的药理学和遗传学研究提供了框架。
