Original Article
Effect of dobutamine on lung aquaporin 5 in endotoxine shock-induced acute lung injury rabbit
Abstract
Background: Dobutamine, a commonly used vasoactive drug, has been reported to reduce pulmonary edema and protect against acute lung injury (ALI) by up-regulating aquaporin 5 (AQP5) expressions. However, the underlying mechanism is still elusive.
Methods: ALI was induced by intravenous injection of LPS. Seventy male New Zealand white rabbits were randomly divided into seven groups: sham group, ALI group, dobutamine low-dose group [group ALI + Dob (L)], dobutamine medium-dose group [group ALI + Dob (M)], dobutamine high-dose group [group ALI + Dob (H)], ALI + Dob (H) + ICI group and sham + ICI group. ICI 118,551, a potent and specific beta-2 antagonist, could block the effect of dobutamine. The animals were sacrificed at 3 h after endotoxic shock and lungs were removed. The arterial blood gas was analyzed. The lung wet to dry (W/D) ratio was determined. The level of cyclic AMP (cAMP) in lung tissue was assessed by ELISA. The expression of AQP5 protein was determined by western blotting and immunohistochemistry. The pathological alteration in lung tissue was evaluated by optical microscopy and electron microscope, and lung injury score was assessed.
Results: Dobutamine increased AQP5 protein expression and cAMP level in a dose-dependent manner. Meanwhile, the degree of lung pathological and ultrastructural lesion was ameliorated and arterial blood gas was improved obviously. Additionally, W/D ratio and histological scores decreased significantly. However, the AQP5 protein expression and cAMP level were significantly decreased in group ALI + Dob (H) + ICI than that in group ALI + Dob (H), the degree of lung pathological and ultrastructural lesion was more serious in group ALI + Dob (H) + ICI than that in group ALI + Dob (H) and the arterial blood gas was not obviously improved.
Conclusions: These results suggested that protective effect of dobutamine against endotoxin shockinduced ALI may be due to its ability of up-regulating AQP5 protein expression via increasing intracellular cAMP concentration.
Methods: ALI was induced by intravenous injection of LPS. Seventy male New Zealand white rabbits were randomly divided into seven groups: sham group, ALI group, dobutamine low-dose group [group ALI + Dob (L)], dobutamine medium-dose group [group ALI + Dob (M)], dobutamine high-dose group [group ALI + Dob (H)], ALI + Dob (H) + ICI group and sham + ICI group. ICI 118,551, a potent and specific beta-2 antagonist, could block the effect of dobutamine. The animals were sacrificed at 3 h after endotoxic shock and lungs were removed. The arterial blood gas was analyzed. The lung wet to dry (W/D) ratio was determined. The level of cyclic AMP (cAMP) in lung tissue was assessed by ELISA. The expression of AQP5 protein was determined by western blotting and immunohistochemistry. The pathological alteration in lung tissue was evaluated by optical microscopy and electron microscope, and lung injury score was assessed.
Results: Dobutamine increased AQP5 protein expression and cAMP level in a dose-dependent manner. Meanwhile, the degree of lung pathological and ultrastructural lesion was ameliorated and arterial blood gas was improved obviously. Additionally, W/D ratio and histological scores decreased significantly. However, the AQP5 protein expression and cAMP level were significantly decreased in group ALI + Dob (H) + ICI than that in group ALI + Dob (H), the degree of lung pathological and ultrastructural lesion was more serious in group ALI + Dob (H) + ICI than that in group ALI + Dob (H) and the arterial blood gas was not obviously improved.
Conclusions: These results suggested that protective effect of dobutamine against endotoxin shockinduced ALI may be due to its ability of up-regulating AQP5 protein expression via increasing intracellular cAMP concentration.
