Mecanismos moleculares envolvidos na modulação do SGLTI pulmonar em modelo murino de sepse experimental

Abstract

Introduction: Respiratory infection can be exacerbated by high glucose concentration in the airway surface liquid (ASL). Objective: the objective of this study was to investigated the role of SGLT activity on ASL glucose concentration and lung of rats with sepsis. Material and methods: Sepsis was induced in rat Wistar male by cecal ligation and puncture surgery (CLP) 24 hours before samples collection. Sham and CLP rats were intranasally treated with saline, salbutamol (to increase SGLT1 activity) or phlorizin (to decrease SGLT1 activity). After 2 hours, animals were anesthetized to analyze ventilation parameters (tidal volume, respiratory rate and minute volume) and collect bronchoalveolar lavage (BAL) and lung. Protein concentration were measured in BAL. Histopathological damages, immunohistochemistry and oxidative stress levels were analyzed in lung. The results were expressed as mean ± SEM and compared with ANOVA/Newman-Keuls test (p< 0.05). Results: Atelectasis and bronchial inflammation were not present in lung of control rats and were present in CLP-sal rats. Salbutamol treatment reduced bronchial inflammation scores and promoted hyperinsuflation in CLP rats. However, phlorizin,increasesd atelectasis, bronchial inflammation and airway damage scores associated with respiratory rate in CLP rats. Sepsis, salbutamol and phlorizin do not change oxidative stress levels, however,the activity of catalase in lung increased in CLP- sal compared with Sham rats. Phlorizin blocked the increase of catalase in CLP rats. The salbutamol also provided the SGLT1 translocation to the plasma membrane of pneumocytes in CLP animals. Conclusion: Taken together, the sepsis promotes atelectasis and lung inflammation associated with increased in antioxidant enzyme catalase. Besides, our data indicate that inhibition of SGLT function with phlorizin increased the severity of atelectasis and bronchial inflammation associated with higher in respiratory rate and inhibition of catalase in lung of CLP rats, suggesting that SGLT could participate in the modulation of earlier stage of septic effects in lung.