Necrostatin-1 can inhibit the necroptosis and improve diaphragm function in the sepsis mice sepsis by cecal ligation and puncture

<bold>Background:</bold> Infection is one of the potential factors of diaphragmatic dysfunction in severe patients. After the occurrence of diaphragm dysfunction, the patient's mechanical ventilation time will be prolonged and the patient's mortality increases. Necroptosis is one of the many ways of death of muscle fibers and may be related to diaphragm dysfunction. <bold>Objective:</bold> This study aims to evaluate the potential diaphragm dysfunction mechanism in sepsis mice. Method Images of the patient's diaphragm were collected. The male C57BL/6 mice are divided into four groups: 1) Sham, 2) Sham + Nec-1,3) CLP + NS and 4) CLP + Nec-1. Evaluate the diaphragm function of the mouse through the diaphragm ultrasound and lung function. Analysis of the expression level of necroptosis in the diaphragm in real time fluorescence quantitative PCR and western blot. <bold>Result:</bold> 35 critical ill patients who had intra-abdominal infection (IAI) exhibited a higher diaphragm echodensity. In the CLP group, the diaphragm function and pulmonary function of mice were significantly reduced. The expression of necroptosis (RIKP1/RIPK3/MLKL) in the diaphragm were increased. After the treatment of necroptosis inhibitors (Nec-1), the diaphragm function and pulmonary function of the mice had improved, and the expression of RIPK1/RIPK3/MLKL declined(Figure 1and 2). <bold>Conclusion:</bold> Diaphragmatic dysfunction is more likely to occur in patients with severe abdominal infections. In the CLP-induced sepsis model, mice have diaphragm dysfunction, and diaphragmatic dysfunction is associated with necroptosis. After giving Nec-1, necroptosis is suppressed, and the diaphragm and respiratory function of mice has been improved.