Small-molecule inhibition of MuRF1 protects against early disuse-induced diaphragmatic dysfunction and atrophy: Underlying cellular and molecular mechanisms

Background: Disuse-induced diaphragmatic dysfunction and atrophy (DIDD) is characterized by a rapid and progressive loss of diaphragm muscle fibers size and contractile function. Patients undergoing mechanical ventilation or diaphragm paralysis can develop DIDD, which correlates with worse clinical outcomes, morbidity and mortality. We hypothesize tha Muscle RING-finger protein-1 (MuRF1) activity plays an important role in DIDD onset and pathophysiology. Aim: To evaluate the effect of small-molecule inhibition of MuRF1 (MyoMed-205) on early DIDD in an experimental model in rats.背景：失用诱导的膈肌功能障碍与萎缩（Disuse-induced diaphragmatic dysfunction and atrophy, DIDD）以膈肌肌纤维体积快速进行性丢失及收缩功能受损为特征。接受机械通气或存在膈肌麻痹的患者可罹患DIDD，该病症与不良临床结局、更高发病率及死亡率密切相关。我们提出假说：肌肉环指蛋白1（Muscle RING-finger protein-1, MuRF1）的活性在DIDD的发病机制与病理生理过程中发挥重要作用。目的：评估小分子抑制MuRF1（MyoMed-205）对大鼠实验模型中早期DIDD的干预效果。