BACKGROUND Lung-protective ventilation (LPV) has been found to minimize the risk of ventilator-induced lung injury (VILI). However, whether LPV is able to diminish ventilator-induced diaphragm dysfunction (VIDD) remains unknown. This study was designed to test the hypothesis that LPV protects the diaphragm against VIDD. METHODS Adult male Wistar rats received either conventional mechanical (tidal volume [VT]: 10 ml/kg, positive end-expiratory pressure [PEEP]: 2 cm H2O; CV group) or lung-protective (VT: 5 ml/kg, PEEP: 10 cm H2O; LPV group) ventilation for 12 h. Then, diaphragms and lungs were collected for biochemical and histological analyses. Transcriptome sequencing (RNA-seq) was performed to determine the differentially expressed genes in the diaphragms between groups. RESULTS Our results suggested that LPV was associated with diminished pulmonary injuries and reduced oxidative stress compared with the effects of the CV strategy in rats. However, animals that received LPV showed increased protein degradation, decreased cross-sectional areas (CSAs) of myofibers, and reduced forces of the diaphragm compared with the same parameters in animals receiving CV (p < 0.05). In addition, the LPV group showed a higher level of oxidative stress in the diaphragm than the CV group (p < 0.05). Moreover, RNA-seq and western blots revealed that the peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), a powerful reactive oxygen species (ROS) inhibitor, was significantly downregulated in the LPV group compared with its expression in the CV group (p < 0.05). CONCLUSIONS Compared with the CV strategy, the LPV strategy did not protect the diaphragm against VIDD in rats. In contrast, the LPV strategy worsened VIDD by inducing oxidative stress together with the downregulation of PGC-1α in the diaphragm. However, further studies are required to determine the roles of PGC-1α in ventilator-induced diaphragmatic oxidative stress.

中文翻译：

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保护肺的通气加重了呼吸机引起的a肌萎缩和无力。

背景技术已经发现肺保护通气（LPV）使呼吸机诱发的肺损伤（VILI）的风险最小化。然而，LPV是否能够减轻呼吸机诱发的diaphragm肌功能障碍（VIDD），仍然未知。这项研究旨在检验LPV保护隔膜免受VIDD侵害的假设。方法成年雄性Wistar大鼠接受常规机械性（潮气量[VT]：10 ml / kg，呼气末正压[PEEP]：2 cm H2O； CV组）或肺保护性（VT：5 ml / kg，PEEP） ：10 cm H2O； LPV组）通风12 h。然后，收集横s和肺进行生化和组织学分析。进行转录组测序（RNA-seq）以确定组之间的隔膜中差异表达的基因。结果我们的结果表明，与CV策略对大鼠的影响相比，LPV与减少的肺部损伤和减少的氧化应激有关。然而，与接受CV的动物相比，接受LPV的动物与相同参数相比，蛋白质降解增加，肌纤维的横截面积（CSA）减少，隔膜的作用力降低（p <0.05）。此外，LPV组在隔膜中的氧化应激水平高于CV组（p <0.05）。此外，RNA-seq和western印迹显示，LPV组过氧化物酶体增殖物激活受体γcoactivator-1alpha（PGC-1α）是一种强大的活性氧（ROS）抑制剂，与其在CV中的表达相比，其表达明显下调组（p <0.05）。结论与简历策略相比，LPV策略不能保护隔膜抵抗大鼠VIDD。相反，LPV策略通过诱导氧化应激以及隔膜中PGC-1α的下调使VIDD恶化。但是，需要进一步的研究来确定PGC-1α在呼吸机诱发的diaphragm肌氧化应激中的作用。