The impact of hindlimb disuse on sepsis-induced myopathy in mice.
The impact of hindlimb disuse on sepsis-induced myopathy in mice.
复制标题
DOI：
10.14814/phy2.14979
复制
发表时间：
2021-07
影响因子：
2.5
通讯作者：
Clanton TL
中科院分区：
文献类型：
--
作者：
Laitano O;Pindado J;Valera I;Spradlin RA;Murray KO;Villani KR;Alzahrani JM;Ryan TE;Efron PA;Ferreira LF;Barton ER;Clanton TL
脓毒症引起以肌肉质量损失和虚弱为特征的肌病。脓毒症患者由于卧床休息而经历长时间的肢体肌肉废用。肢体肌肉废用对肌病表型的贡献仍然很少描述。为了表征伴有后肢废用的脓毒症诱导的肌病，我们将通过盲肠结扎穿孔（CLP）的经典脓毒症模型与小鼠后肢悬挂（HLS）的废用模型结合起来。雄性C57 bl/6 j小鼠经历CLP或SHAM手术。手术后4天，小鼠接受HLS或正常Ambassador（NA）7天。解剖比目鱼肌（SOL）和趾长伸肌（EDL）进行体外肌肉力学、形态学和组织学评估。在SOL肌肉中，CLP+NA和SHAM+HLS条件均引起比力降低约20%（p < 0.05）。当组合时，CLP+HLS引起比力降低约35%（p < 0.05）。仅在CLP+HLS小鼠的EDL肌肉中最大比力的损失（~8%）是明显的（p < 0.05）。CLP+HLS降低SOL中的肌纤维横截面积（CSA）和质量（p < 0.05）。在EDL肌肉中，CLP+HLS在较小程度上降低了绝对质量（p < 0.05），而CSA没有变化。免疫组织化学显示CLP+HLS小鼠SOL中有大量髓样细胞浸润（CD 68+），但在EDL肌肉中没有（p < 0.05）。CLP与HLS组合是研究脓毒症诱导的小鼠肌病的可行模型。后肢废用与脓毒症相结合，以肌肉依赖的方式诱导肌肉功能障碍和免疫细胞浸润。这些发现强调了脓毒症宿主康复干预的重要性，以防止肌肉废用，并有助于减轻肌病。本研究显示了骨骼肌废用对小鼠脓毒症诱导的肌病的影响。使用Biorender软件开发。
Sepsis induces a myopathy characterized by loss of muscle mass and weakness. Septic patients undergo prolonged periods of limb muscle disuse due to bed rest. The contribution of limb muscle disuse to the myopathy phenotype remains poorly described. To characterize sepsis‐induced myopathy with hindlimb disuse, we combined the classic sepsis model via cecal ligation and puncture (CLP) with the disuse model of hindlimb suspension (HLS) in mice. Male C57bl/6j mice underwent CLP or SHAM surgeries. Four days after surgeries, mice underwent HLS or normal ambulation (NA) for 7 days. Soleus (SOL) and extensor digitorum longus (EDL) were dissected for in vitro muscle mechanics, morphological, and histological assessments. In SOL muscles, both CLP+NA and SHAM+HLS conditions elicited ~20% reduction in specific force (p < 0.05). When combined, CLP+HLS elicited ~35% decrease in specific force (p < 0.05). Loss of maximal specific force (~8%) was evident in EDL muscles only in CLP+HLS mice (p < 0.05). CLP+HLS reduced muscle fiber cross‐sectional area (CSA) and mass in SOL (p < 0.05). In EDL muscles, CLP+HLS decreased absolute mass to a smaller extent (p < 0.05) with no changes in CSA. Immunohistochemistry revealed substantial myeloid cell infiltration (CD68+) in SOL, but not in EDL muscles, of CLP+HLS mice (p < 0.05). Combining CLP with HLS is a feasible model to study sepsis‐induced myopathy in mice. Hindlimb disuse combined with sepsis induced muscle dysfunction and immune cell infiltration in a muscle dependent manner. These findings highlight the importance of rehabilitative interventions in septic hosts to prevent muscle disuse and help attenuate the myopathy. This study shows the impact of skeletal muscle disuse on sepsis‐induced myopathy in mice. Developed with Biorender software.
登录
查看更多内容
影响因子：
4.6
作者：
Laitano O;Robinson GP;Murray KO;Garcia CK;Mattingly AJ;Morse D;King MA;Iwaniec JD;Alzahrani JM;Clanton TL
通讯作者：
Clanton TL
影响因子：
4
作者：
Kalamgi RC;Larsson L
通讯作者：
Larsson L
影响因子：
7.3
作者：
Kawasaki T;Kawai T
通讯作者：
Kawai T
影响因子：
4.8
作者：
Fay, Katherine T.;Klingensmith, Nathan J.;Coopersmith, Craig M.
通讯作者：
Coopersmith, Craig M.
影响因子：
8.8
作者：
Maes, Karen;Stamiris, Angela;Gayan-Ramirez, Ghislaine
通讯作者：
Gayan-Ramirez, Ghislaine