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Effects of resolvin D1 on inflammatory responses and oxidative stress of lipopolysaccharide-induced acute lung injury in mice

         

摘要

Background A variety of inflammatory mediators and effector cells participate together in acute lung injury,and lead to secondary injury that is due to an inflammatory cascade and secondary diffuse lung parenchyma injury.Inflammation is associated with an oxidative stress reaction,which is produced in the development of airway inflammation,and which has positive feedback on inflammation itself.Resolvin D1 can reduce the infiltration of neutrophils,regulate cytokine levels and reduce the inflammation reaction,and thereby promote the resolution of inflammation.The purpose of this study is to investigate the effects of resolvin D1 on an inflammatory response and oxidative stress during lipopolysaccharide (LPS)-induced acute lung injury.Methods LPS (3 mg/kg) was used to induce the acute lung injury model.Pretreatment resolvin D1 (100 ng/mouse) was given to mice 30 minutes before inducing acute lung injury.Mice were observed at 6 hours,12 hours,1 day,2 days,3 days,4 days and 7 days after LPS was administrated,then they were humanely sacrificed.We collected bronchoalveolar lavage fluid (BALF) and the lung tissues for further analysis.Paraffin section and HE staining of the lung tissues were made for histopathology observations.Parts of the lung tissues were evaluated for wet-to-dry (W/D) weight ratio.tumor necrosis factor (TNF)-α,inter leukin (IL)-1β,IL-10 and myeloperoxidase (MPO) were detected by enzyme-linked immunosorbent assay (ELISA).A lipid peroxidation malondialdehyde (MDA) assay kit was used to detect MDA.A total superoxide dismutase assay kit with WST-1 was used to analyze superoxide dismutase (SOD).We determined the apoptosis of neutrophils by Flow Cytometry.A real-time quantitative PCR Detecting System detected the expression of mRNA for heme oxygenase (HO)-1.Results Pretreatment with resolvin D1 reduced the pathological damage in the lung,decreased the recruitment of neutrophils and stimulated their apoptosis.It markedly decreased the expressions of TNF-α,IL-1β and increased the expressions of IL-10,and decreased the production of MDA and increased the expressions of SOD.The mRNA expression of HO-1 was also significantly increased.Conclusions Resolvin D1 displays potent anti-inflammatory actions by regulating cytokines,inhibiting aberrant neutrophil recruitment and stimulating apoptosis of neutrophils.Resolvin D1 can also relieve the injury due to oxidative stress.The mechanisms might be related to increase HO-1 expression.

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  • 来源
    《中华医学杂志(英文版)》 |2014年第5期|803-809|共7页
  • 作者单位

    Department of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan, Hubei 430022, China;

    Department of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan, Hubei 430022, China;

    Department of Anesthesiology, Shenzhen People's Hospital, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, China;

    Department of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan, Hubei 430022, China;

    Department of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan, Hubei 430022, China;

    Department of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan, Hubei 430022, China;

    Department of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan, Hubei 430022, China;

    Department of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,Wuhan, Hubei 430022, China;

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