BACKGROUND Profound skeletal muscle wasting and weakness is common after severe burn and persists for years after injury contributing to morbidity and mortality of burn patients. Currently, no ideal treatment exists to inhibit muscle catabolism. Metformin is an anti-diabetic agent that manages hyperglycemia but has also been shown to have a beneficial effect on stem cells after injury. We hypothesize that metformin administration will increase protein synthesis in the skeletal muscle by increasing the proliferation of muscle progenitor cells, thus mitigating muscle atrophy post-burn injury. METHODS To determine whether metformin can attenuate muscle catabolism following burn injury, we utilized a 30% total burn surface area (TBSA) full-thickness scald burn in mice and compared burn injuries with and without metformin treatment. We examined the gastrocnemius muscle at 7 and 14 days post-burn injury. RESULTS At 7 days, burn injury significantly reduced myofiber cross-sectional area (CSA) compared to sham, p < 0.05. Metformin treatment significantly attenuated muscle catabolism and preserved muscle CSA at the sham size. To investigate metformin's effect on satellite cells (muscle progenitors), we examined changes in Pax7, a transcription factor regulating the proliferation of muscle progenitors. Burned animals treated with metformin had a significant increase in Pax7 protein level and the number of Pax7-positive cells at 7 days post-burn, p < 0.05. Moreover, through BrdU proliferation assay, we show that metformin treatment increased the proliferation of satellite cells at 7 days post-burn injury, p < 0.05. CONCLUSION In summary, metformin's various metabolic effects and its modulation of stem cells make it an attractive alternative to mitigate burn-induced muscle wasting while also managing hyperglycemia.

中文翻译：

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二甲双胍通过增加Pax7阳性的肌肉祖细胞来减轻热损伤后的肌肉浪费。

背景技术严重烧伤后骨骼肌严重浪费和无力，并在受伤后持续多年，导致烧伤患者的发病率和死亡率。当前，不存在抑制肌肉分解代谢的理想疗法。二甲双胍是一种抗糖尿病药，可控制高血糖症，但也已显示对损伤后的干细胞具有有益作用。我们假设二甲双胍的给药将通过增加肌肉祖细胞的增殖来增加骨骼肌中的蛋白质合成，从而减轻烧伤后的肌肉萎缩。方法为了确定二甲双胍是否可以减轻烧伤后的肌肉分解代谢，我们利用30％的总烧伤表面积（TBSA）全层烫伤烧伤，比较了有和无二甲双胍治疗的烧伤。我们在烧伤后第7天和第14天检查了腓肠肌。结果与假手术相比，在第7天，烧伤使肌纤维横截面积（CSA）明显减少，p <0.05。二甲双胍治疗可显着减弱肌肉分解代谢，并在假手术时保留肌肉CSA。为了研究二甲双胍对卫星细胞（肌肉祖细胞）的作用，我们检查了Pax7的变化，Pax7是调节肌肉祖细胞增殖的转录因子。用二甲双胍治疗的烧伤动物在烧伤后第7天Pax7蛋白水平和Pax7阳性细胞数量显着增加，p <0.05。此外，通过BrdU增殖测定，我们显示二甲双胍治疗可增加烧伤后7天卫星细胞的增殖，p <0.05。结论总的来说，二甲双胍