Dexmedetomidine alleviates pulmonary edema by upregulating AQP1 and AQP5 expression in rats with acute lung injury induced by lipopolysaccharide.

Abstract

This study aims to elucidate the mechanisms by which dexmedetomidine alleviates pulmonary edema in rats with acute lung injury induced by lipopolysaccharide (LPS). Male Wistar rats were randomly divided into five groups: normal saline control (NS) group, receiving intravenous 0.9% normal saline (5 mL/kg); LPS group, receiving intravenous LPS (10 mg/kg); small-dose dexmedetomidine (S) group, treated with a small dose of dexmedetomidine (0.5 μg · kg(-1) · h(-1)); medium-dose dexmedetomidine (M) group, treated with a medium dose of dexmedetomidine (2.5 μg · kg(-1) · h(-1)); high-dose dexmedetomidine (H) group, treated with a high dose of dexmedetomidine (5 μg · kg(-1) · h(-1)). The rats were sacrificed 6 h after intravenous injection of LPS or NS, and the lungs were removed for evaluating histological characteristics and determining the lung wet/dry weight ratio (W/D). The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) in the lung tissues were assessed by enzyme- linked immunosorbent assay (ELISA). The mRNA and protein expression levels of aquaporin-1 (AQP1) and aquaporin-5 (AQP5) were detected by RT-PCR, immunohistochemistry, and Western blotting. The lung tissues from the LPS groups were significantly damaged, which were less pronounced in the H group but not in the small-dose dexmedetomidine group or medium-dose dexmedetomidine group. The W/D and the concentrations of TNF-α and IL-1β in the pulmonary tissues were increased in the LPS group as compared with those in NS group, which were reduced in the H group but not in S group or M group (P<0.01). The expression of AQP1 and AQP5 was lower in the LPS group than in the NS group, and significantly increased in the H group but not in the S group or M group (P<0.01). Our findings suggest that dexmedetomidine may alleviate pulmonary edema by increasing the expression of AQP-1 and AQP-5.