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烧伤会导致斯普拉格-道利大鼠出现严重的肌肉蛋白质消耗,使用脂肪分解抑制剂阿西莫司并不能解决这一问题。

Burns results in profound muscle protein wasting in Sprague Dawley rats that is not resolved using the lipolysis inhibitor, acipimox.

作者信息

Vardarli Emre, Bhattarai Nisha, El Ayadi Amina, Prasai Anesh, Rontoyanni Victoria G, Reda Abdelrahman Doaa, Murton Andrew J

机构信息

Graduate School of Biomedical Sciences, The University of Texas Medical Branch, Galveston, Texas, United States of America.

Department of Surgery, The University of Texas Medical Branch, Galveston, Texas, United States of America.

出版信息

PLoS One. 2025 May 20;20(5):e0323640. doi: 10.1371/journal.pone.0323640. eCollection 2025.

Abstract

INTRODUCTION

Major burns results in the rapid and profound accumulation of lipid in peripheral tissues, but its impact on muscle metabolic function is unclear. Given previous reports demonstrating that lipid oversupply compromises processes instrumental in the maintenance of muscle protein balance, we hypothesize that burn-induced lipid accumulation contributes to the loss of muscle mass with thermal injury.

METHODS

To investigate this further, 48 male Sprague Dawley rats were randomized to undergo either a 60% total body surface area burn or sham procedure. To elucidate the impact of burn-induced lipid accumulation, animals were further subdivided to receive either acipimox (50 mg.kg-1 b.w.), a lipolysis inhibitor administered to deplete intramuscular lipids, or vehicle (PBS), daily for 7 days. Throughout, animals received deuterated water to permit the determination of muscle protein kinetics.

RESULTS

Compared to sham animals, burn injury resulted in a 12% loss of gastrocnemius muscle mass (P < 0.001), paralleled by a 30 and 40 increase in the fractional synthetic and breakdown rates of gastrocnemius mixed proteins (P < 0.01), respectively, culminating in a 2-fold decline in net muscle protein (P < 0.01). Contrary to expectations, burns had no impact on muscle triglyceride content, while acipimox treatment failed to protect muscle mass, impact muscle triglyceride concentrations, or muscle protein kinetics.

CONCLUSIONS

In a rodent model of burns, the loss of muscle mass primarily occurs due to the acceleration of muscle proteolysis, independent of any change in muscle lipid content.

摘要

引言

大面积烧伤会导致外周组织中脂质迅速大量蓄积,但其对肌肉代谢功能的影响尚不清楚。鉴于先前的报道表明脂质供应过剩会损害维持肌肉蛋白质平衡的重要过程,我们推测烧伤诱导的脂质蓄积会导致热损伤后肌肉质量的丧失。

方法

为进一步研究这一问题,将48只雄性Sprague Dawley大鼠随机分为两组,分别接受60%体表面积烧伤或假手术。为阐明烧伤诱导的脂质蓄积的影响,将动物进一步细分,每天给予阿昔莫司(50mg·kg-1体重),一种用于消耗肌肉内脂质的脂肪分解抑制剂,或给予赋形剂(PBS),持续7天。在此期间,动物饮用氘代水以测定肌肉蛋白质动力学。

结果

与假手术动物相比,烧伤导致腓肠肌质量损失12%(P<0.001),同时腓肠肌混合蛋白的合成率和分解率分别增加30%和40%(P<0.01),最终导致肌肉净蛋白下降2倍(P<0.01)。与预期相反,烧伤对肌肉甘油三酯含量没有影响,而阿昔莫司治疗未能保护肌肉质量、影响肌肉甘油三酯浓度或肌肉蛋白质动力学。

结论

在烧伤的啮齿动物模型中,肌肉质量的丧失主要是由于肌肉蛋白水解加速,与肌肉脂质含量的任何变化无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ab/12091881/15be605afd1b/pone.0323640.g001.jpg

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