Study On Molecular Mechanism Of Sustained Inflation In Acute Respiratory Distress Syndrome

Object:The aim of this study is to investigate the effect and the possible molecular mechanism of sustained inflation (SI) recruitment maneuvers (RM) in acute respiratory distress syndrome (ARDS) Beagle dogs following closed endotracheal suctioning.Method:Twenty Beagle dogs were induced into the models of ARDS with oleic acid and were mechanically ventilated. They were randomized into two groups (Non-SI-group and SI-group) when the ARDS models were stable for thirty minutes. Non-SI-group:no SI was applied to ARDS dogs following closed endotracheal suctioning. SI-group:SI was applied to ARDS dogs following closed endotracheal suctioning. To implement SI the mode of continuous positive airway pressure (CPAP) was used and CPAP was set at30cm H2O for30seconds. After SI, the basic ventilation was resumed. Oxygenation, indexes of respiratory mechanics and hemodynamic indexes were serially measured during the procedure (before closed endotracheal suctioning,3min,15min,30min,60min,120min and240min after closed endotracheal suctioning respectively). The serum was collected before and after modeling ARDS, an hour and4hours after endotracheal suctioning. The serum protein level of TNF-α, IL-1β, IL-6, IL-10, SP-A and HMGB1were measured by ELISA. Four hours after endotracheal suctioning, the ARDS dogs were sacrificed. The expression of AQP-1, AQP-5, SP-A, HMGB1, FLIP and IL-6mRNA in the lung tissue were measured by RT-PCR.Results:SI in ARDS improved PaO2, Cst and reduced the airway resistance but had no significant effect on the hemodynamic indexes. At molecular level, SI in ARDS decreased the serum level of proinflammatory cytokines (TNF-α, IL-1β, IL-6) and anti-inflammatory cytokine (IL-10)(P<0.05). In the lung tissue, SI in ARDS increased the expression of AQP-1, AQP-5, and FLIP mRNA and decreased the expression of IL-6mRNA (P<0,05). As for HMGB1, there was no significant difference between SI group and non-SI group in both serum and lung tissue. Conclusions:SI can safely improve oxygenation, lung compliance and hypoxemia after endotracheal suctioning. The possible molecular mechanism was SI relieved the inflammatory reaction by decreasing the secretion of related inflammatory factors and thus reduced the loss of SP-A, increased the expression of AQP-1, AQP-5in the lung accordingly. SI might also up-regulate apoptosis inhibitory protein to inhibit the apoptosis of pulmonary capillary endothelium and alveolar epithelium. All these changes might be associated with alleviation of pulmonary edema and the improvement of alveolocapillary barrier which contributed to improved oxygenation and lung compliance.