Rinkinen Jacob, Hwang Charles D, Agarwal Shailesh, Oluwatobi Eboda, Peterson Jonathan, Loder Shawn, Brownly Robert C, Cummings Timothy, Cederna Paul S, Levi Benjamin
Ann Arbor, Mich. From the Department of Surgery, Section of Plastic Surgery, University of Michigan.
Plast Reconstr Surg. 2015 Nov;136(5):612e-623e. doi: 10.1097/PRS.0000000000001723.
By understanding the global inflammatory effects on distant myopathies, surgeons can better guide the rehabilitative process for burn patients. The authors tested the systemic effect of burn injury on distant injured muscle and native bone using immunohistochemistry and validated a new morphometric analytic modality to reproducibly quantify muscle atrophy using computed tomographic imaging.
In vivo studies were performed on C57/BL6 mice using an Achilles tenotomy with concurrent burn injury model. Total muscle and bone (tibia and fibula) volume/density were quantified near the site of Achilles tenotomy using micro-computed tomography at 5, 7, and 9 to 12 weeks after surgery. The impact of burn injury on the inflammatory cascade [nuclear factor (NF)-κB, p-NF-κB] and the interconnected protein catabolism signaling pathway (Atrogin-1) was assessed by immunohistochemistry.
Muscle volume and density at the site of Achilles tenotomy in burned mice were significantly diminished compared with nonburned mice at 5 weeks and 9 to 12 weeks. Similar decreases in muscle volume and density were observed when comparing tenotomy to no tenotomy. Cortical bone health remained stable in burn/tenotomy mice compared with tenotomy. Muscle atrophy was associated with up-regulation of p-NF-κB, NF-κB, and Atrogin-1 assessed by immunohistochemistry.
Burn injury significantly decreases muscle volume and density. Increased muscle atrophy using our computed tomographic morphometric analysis correlated with a significant increase in intramuscular inflammatory markers and proteolysis enzymes. This study demonstrates a unique characterization of how burn injuries may worsen local myopathy. Moreover, it provides a novel approach for quantifying muscle atrophy over an expanded period.
通过了解全身性炎症对远处肌病的影响,外科医生可以更好地指导烧伤患者的康复过程。作者使用免疫组织化学方法测试了烧伤对远处受伤肌肉和天然骨骼的全身影响,并验证了一种新的形态计量分析方法,以通过计算机断层扫描成像可重复地量化肌肉萎缩。
使用跟腱切断术并发烧伤损伤模型对C57/BL6小鼠进行体内研究。在手术后5、7和9至12周,使用微型计算机断层扫描在跟腱切断术部位附近量化总肌肉和骨骼(胫骨和腓骨)的体积/密度。通过免疫组织化学评估烧伤对炎症级联反应[核因子(NF)-κB、p-NF-κB]和相互关联的蛋白质分解代谢信号通路(Atrogin-1)的影响。
与未烧伤小鼠相比,烧伤小鼠在5周以及9至12周时跟腱切断术部位的肌肉体积和密度显著减小。与未进行跟腱切断术相比,进行跟腱切断术时也观察到类似的肌肉体积和密度下降。与单纯跟腱切断术小鼠相比,烧伤/跟腱切断术小鼠的皮质骨健康状况保持稳定。通过免疫组织化学评估,肌肉萎缩与p-NF-κB、NF-κB和Atrogin-1的上调相关。
烧伤显著降低肌肉体积和密度。使用我们的计算机断层扫描形态计量分析发现,肌肉萎缩增加与肌肉内炎症标志物和蛋白水解酶的显著增加相关。本研究揭示了烧伤如何使局部肌病恶化的独特特征。此外,它提供了一种在更长时期内量化肌肉萎缩的新方法。