Resolvin D1Reduces Deterioration Of Tight Junction Proteins By Up-regulating HO-1in LPS-induced Mice

Objective：The purpose of this study is to investigate the effects and mechanism of RvD1on the disruption of tight junction protein that results in the permeability edema in a modelof Lipopolysaccharide (LPS) induced ALI.Methods：We used lipopolysaccharide (3mg/kg) induced the acute lung injury model.Pretreat with Znpp (50mg/kg) and Resolvin D1(5μg/kg) to mice60and30minutes beforeinducing ALI respectively. Mice were observed to24h after LPS was administrated, andthen they were humanely killed. Collecting bronchoalveolar lavage fluid (BALF) and thelung tissues for further analysis. Paraffin section and HE dyeing of the lung tissues were forhistopathology observations; part of the lung tissue were put in oven for W/D ratios;Expressions of tight junction proteins (TJs) occludin and ZO-1were examined byimmunofluorescence staining and western blot; mRNA in lung tissue was studied by realtime-PCR; the TUNEL kit was performed for the detection of apoptosis of pulmonarybarrier.Results：24hours after LPS inhaled by mice, pretreatment to mice by RvD1can improvethe pathological changes of the lung. The wet-to-dry rate indicated that pretreatment withRvD1relieved the pulmonary edema and pulmonary capillary permeability. Moreover,RvD1attenuated the LPS-induced deterioration of tight junction protein zona occludin-1(ZO-1) and Occludin significantly. And we found RvD1increased Haeme oxygenase-1(HO-1) expression contributed to the protection on the deterioration of TJs. In addition, wefound RvD1could reduce pulmonary cellular apoptosis in LPS-induced mice.Conclusion：The data suggest that there is potential benefit of RvD1in protecting the lungfrom acute lung injury.Resolvin D1possesses the ability that relieves the pulmonary edema and restores pulmonary capillary permeability, and reduces disruption of TJs in LPSinduced acute lung injury of mice at least in part by up-regulating HO-1expression.