| The clinical criteria for acute lung injury(ALI)are bilateral acute lung infiltrates with hypoxemia and no evidence of hydrostatic pulmonary edema.The clinical manifestations of severe ALI are collectively referred to as acute respiratory distress syndrome(ARDS),which is a clinical syndrome characterized by acute hypoxic respiratory failure,infiltrative pulmonary edema in both lungs,and normal cardiac filling pressures.Clinical factors that induce ALI include sepsis,pneumonia,et al.The survival rate of ALI has been improved by improving lung-protective ventilatory support,but studies have shown that incorrect mechanical ventilation also leads to ALI.Animal models are critical for studying ALI/ARDS.Due to the complexity of the disease,a single ALI animal model cannot capture all the disease features of human ALI/ARDS.The histopathological features of human ALI/ARDS are neutrophilic alveolitis,alveolar epithelial and endothelial damage,hyaline membrane formation,and microvascular thrombosis.Numerous studies on the alveolar-capillary barrier in ALI have shown that the destruction of vascular endothelial cells plays an important role in ALI/ARDS.The SOXF subfamily of the SOX(SRY-Related HMG Box)transcription factor family includes SOX7,SOX17,and SOX18,which are key regulators of the development of the cardiovascular system and play an important role in endothelial cells.SOXF were reported to have significant functional complementarity.Identifying changes in SOXF factors in various models of lung injury is important to reveal their role in lung injury.The purpose of this study was to explore the expression changes of SOXF family transcription factors in animal models of lung injury caused by different factors.Therefore,we established the rat cecal ligation and puncture model,rat ventilator-induced lung injury model,mouse cecal ligation and puncture combined with mechanical ventilation model,h ACE2 KI mouse+RBD/S1 models.The degree of lung injury in the model was judged by the number of cells and total protein concentration in BALF(bronchial alveolar lavage fluid),the lung injury fraction,and the positive rate of MPO(myeloperoxidase)in the lung;and the expression changes of proteins SOX7,SOX17,and SOX18 in the model lung tissue were detected.The results are as follows:1.The number of neutrophils in the blood of the sepsis model in rats 6 hours after severe cecal ligation and puncture increased significantly,the number of cells and total protein concentration in BALF,the lung injury score and the positive rate of MPO in the lung increased significantly;The expressions of SOX7,SOX17 and SOX18 were all decreased.2.After the rats were ventilated with 40ml/kg tidal volume for 4 hours,the cell number and total protein concentration in BALF,lung injury score and lung MPO positive rate were significantly increased.The expressions of SOX7,SOX17 and SOX18 in lung tissue were decreased.3.The mouse model of sepsis was established 6 hours after severe cecal ligation and puncture.The number of cells and total protein concentration in the BALF,the lung injury score and the positive rate of MPO in the lung did not change significantly.However,4hours after cecal ligation and puncture,and 2 hours after 40ml/kg high-pressure mechanical ventilation,the cell number and total protein concentration in BALF,lung injury score and lung MPO positive rate were significantly increased.The expressions of SOX7,SOX17 and SOX18 in the lung tissue of the mouse CLP+VILI model were all decreased.4.h ACE2 KI mice were given Spike RBD protein or S1 protein for 10 days to induce lung injury.Compared with h ACE2KI+RBD group,the number of cells and total protein concentration in the BALF,the lung injury score and the positive rate of MPO in the lungs of h ACE2KI+S1 group increased more significantly.In the lung tissue of h ACE2KI+RBD mice,the expressions of SOX7 and SOX18 did not change significantly,but SOX17 decreased significantly.However,in the lung tissue of h ACE2KI+S1 mice,the expressions of SOX7 and SOX17 were significantly decreased,while the expression of SOX18 was increased.In conclusion,in this study,a variety of animal models of lung injury were established and the expression of SOXF family proteins were detected.The expression of SOXF family proteins in the lung tissues of several acute lung injury models established within a few hours was significantly decreased,while the expression changes in the lung injury models established within a few days were different. |
