肺上皮細胞でのaquaporin-5高発現は上皮細胞のアポトーシスを抑制することで敗血症に伴う肺水腫を抑制する

抄録

The development of acute respiratory syndrome (ARDS) during sepsis clinically doubles the mortality rate of patients. ARDS is essentially non-cardiogenic pulmonary edema, based on increasing permeability of vascular endothelial and pulmonary epithelial cells due to their injury and cell death caused by excessive inflammation in lung. It has been also known that the expression of AQP5 in lung tissues is considerably reduced in LPS induced ARDS mouse model. Therefore, it is possible that the decrease in AQP5 expression contributes to the pathogenesis of ARDS. We have established a transgenic (Tg) mouse in which AQP5 is highly expressed specifically in the pulmonary epithelial cells. In this study, we have examined the significance of changes in AQP5 expression in ARDS, using this Tg mice. In wild type (WT) mice, intraperitoneal treatment of LPS decreased survival rate and caused pulmonary edema evaluated by lung wet/dry weight ratio. In AQP5-Tg mice, the decrease in survival rate and pulmonary edema caused by LPS was considerably improved. In addition, TUNEL stained lung tissue revealed that the apoptotic cells in AQP5-Tg mice was significantly less than that in WT mice. These results indicated that the decrease in AQP5 expression in ARDS enhances the apoptosis of pulmonary epithelial cells and exacerbate pulmonary edema.