肌营养不良模型（mdx）小鼠的呼吸机相关性膈肌功能障碍。
Ventilator-induced diaphragmatic dysfunction in MDX mice.
机构信息
Meakins-Christie Laboratories, and Translational Research in Respiratory Diseases Program, McGill University Health Centre and Research Institute, 1001 Decarie Boulevard, Montreal, Quebec, H4A 3J1, Canada.
Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
出版信息
Muscle Nerve. 2018 Mar;57(3):442-448. doi: 10.1002/mus.25760. Epub 2017 Aug 25.
INTRODUCTION
Patients with Duchenne muscular dystrophy (DMD) frequently undergo mechanical ventilation (MV) for treatment of hypoventilation, but the susceptibility of the dystrophic diaphragm to ventilator-induced diaphragmatic dysfunction (VIDD) has not been examined.
METHODS
Dystrophic mice (mdx-genetic homolog of DMD) were assigned to non-ventilated control (CTL) and MV (for 6 hours) groups. Biochemical markers of oxidative/cellular stress, metabolism, and proteolysis were compared along with ex-vivo diaphragmatic force production.
RESULTS
MV significantly depressed maximal diaphragmatic force production compared with baseline values. In addition, MV triggered oxidative stress responses, STAT3 phosphorylation, and an upregulation of cellular pathways associated with muscle proteolysis and/or wasting (autophagy, E3 ubiquitin ligases, and myostatin).
DISCUSSION
Short-term MV induces rapid diaphragmatic force loss and biochemical changes consistent with VIDD in mdx mice. This may have implications for the optimal use of intermittent MV in DMD patients. Muscle Nerve 57: 442-448, 2018.
简介
杜氏肌营养不良症（DMD）患者常因呼吸功能不全而接受机械通气（MV）治疗，但尚未研究营养不良性膈肌对呼吸机引起的膈肌功能障碍（VIDD）的易感性。
方法
将营养不良的小鼠（DMD 的基因同源物 mdx）分为非通气对照（CTL）和 MV（6 小时）组。比较了氧化/细胞应激、代谢和蛋白水解的生化标志物，以及体外膈肌的肌力产生。
结果
MV 与基线相比显著降低了最大膈肌肌力。此外，MV 引发了氧化应激反应、STAT3 磷酸化以及与肌肉蛋白水解和/或消耗（自噬、E3 泛素连接酶和肌肉生长抑制素）相关的细胞途径的上调。
讨论
短期 MV 在 mdx 小鼠中引起迅速的膈肌肌力丧失和生化变化，与 VIDD 一致。这可能对 DMD 患者间歇性 MV 的最佳应用有影响。肌肉神经 57:442-448,2018。
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