| Objective:The aim of the study was to investigate the involvement of aquaporin-1,3 or 5(AQP1,3,5) in murine model of lipopolysaccharide(LPS)-induced acute lung injury(ALI),and the prective effects of dexamethasone(DXM) on ALI. Furthermore,the activities of cAMP were assayed in order to investigate the mechenisms of aquaporin-1,3 and 5 played in ALI.Methods:ALI was induced by intra-tracheal injection of LPS(4 mg.kg-1) in the mouse from the ALI.Mice were injected DXM(0.5 mg·kg-1) via tail vein 10 min before and 3 hours after injection of LPS.The wet lung weight to dry lung weight ratio(W/D), pulmonary permeability index(PPI),white blood cell(WBC) and neutrophilic granulocyte in the bronchoalveolar lavage fluid(BALF) were measured after 6 hours of injection of LPS,as well as the concentration of tumor necrosis factor(TNF)-alpha and IL-1βin the BALF were detected by enzyme-linked immunosorbent assay (ELISA).The pulmonary pathology was observed under microscopy.The mRNA expression aquaporin-1,3 or 5 in the mouse lung detected by Real-Time PCR.The activities of cAMP in the lung were assayed by ELISA.Results:1.The W/D ratio of LPS group(4.67±0.37) was higher than those of control group(4.07±0.30,p＜0.01) and those of Dex-treated group(4.13±0.31,p＜0.01).The PPI of LPS group(8.82±1.48) was obviously higher than those of control group(4.61±0.78,p＜0.01) and those of Dex-treated group(5.46±1.25,p＜0.01).DXM alleviated ALI induced by LPS.2.The number of WBC and neutrophilic granulocyte,the concentration of TNF-alpha and IL-1βin lung BALF were significantly increased in the LPS group than those of control group(P＜0.05)or Dex-treated group(P＜0.01).3. Pathological examination of the lung tissues showed that the LPS group characterized by consistent with increased lung vascular permeability,neutrophil infiltration and edema formation.However,edema formation,lung vascular permeability of the Dex-treated group lung was not observed.Furthermore,histological lung injury score of the LPS group(4.8±0.4) was significantly higher than those of control group (0.2±0.1,P＜0.05) and Dex-treated group(1.9±0.3,P＜0.05).4.The expression of mRNA of AQP1 and AQP5 in LPS groups revealed a notable decline as compared with the control group(P＜0.01) and Dex-treated group(P＜0.01),however,there was no significantly difference among the three groups on AQP3 mRNA level(P＞0.05).5.The activities of cAMP of the LPS group were lower than those of control group(P＜0.05) and those of Dex-treated group(P＜0.05).conclusions:1.DXM that given by tail vein previously alleviated inflammation in the murine lung induced by LPS.2.AQP1 and AQP5 mRNA expression,which facilitates fluid transport,defining the effect of AQP1 and AQP5 on lung edema formation,were decreased in LPS induced ALI.Consequently,we suggested that DXM alleviated inflammation induced by LPS by up-regulation of AQP1 and AQP5 expression.3.The mouse in the LPS group had a lower cAMP compared with the control group and Dex-treated group,which was in line with AQP1 and AQP5 expression.This fact indicated that cAMP probably also involved in regulation of AQP1 and of AQP5 of ALI.4.In contrast,it seemed that AQP3 may not involve in formation of pulmonary edema. |
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