Ischemic postconditioning attenuates lung reperfusion injury and reduces systemic proinflammatory cytokine release via heme oxygenase 1.

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  • Author(s): Xu B;Xu B; Gao X; Xu J; Lei S; Xia ZY; Xu Y; Xia Z
  • Source:
    The Journal of surgical research [J Surg Res] 2011 Apr; Vol. 166 (2), pp. e157-64. Date of Electronic Publication: 2010 Dec 21.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Academic Press Country of Publication: United States NLM ID: 0376340 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1095-8673 (Electronic) Linking ISSN: 00224804 NLM ISO Abbreviation: J Surg Res Subsets: MEDLINE
    • Publication Information:
      Publication: New York, NY : Academic Press
      Original Publication: Philadelphia [etc.]
    • Subject Terms:
      Cytokines/*blood ; Heme Oxygenase (Decyclizing)/*metabolism ; Ischemic Preconditioning/*methods ; Reperfusion Injury/*immunology ; Reperfusion Injury/*prevention & control; Animals ; Blood Gas Analysis ; Female ; Heme Oxygenase (Decyclizing)/immunology ; Interleukin-6/blood ; Interleukin-8/blood ; Lung/immunology ; Lung/pathology ; Male ; Neutrophils/immunology ; Organ Size ; Peroxidase/metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/pathology ; Tumor Necrosis Factor-alpha/blood
    • Abstract:
      Objective: Systemic inflammatory response following ischemia-reperfusion injury (IRI) to a specific organ may cause injuries in multiple remote organs. The emergence of ischemic postconditioning (IPO) provides a potential method for experimentally and clinically attenuating various types of organ postischemic injuries. We have shown that IPO can attenuate lung IRI by up-regulating the protein expression of heme oxygenase-1(HO-1). This study tested the hypothesis that IPO attenuates systemic inflammatory responses following lung IRI by activating HO-1.
      Methods: Anaesthetized and mechanically ventilated adult Sprague-Dawley rats were randomly assigned to one of the following groups (n = 8 each): the sham-operated control group, the ischemia-reperfusion (IR) group (40 min of left-lung ischemia and 120 min of reperfusion), the IPO group (three successive cycles of 30-s reperfusion per 30-s occlusion before restoring full perfusion), and the zinc protoporphyrin IX (ZnP) plus IPO group (ZnP, an inhibitor of HO-1, was injected intraperitoneally at 20 mg/kg 24 h prior to the experiment, and the rest of the procedures were similar to that of the IPO group). Lung injury was assessed by arterial blood gas analysis, wet-to-dry lung weight ratio and tissue histologic and biochemical changes. The lung tissue and plasma levels of lipid peroxidation were determined by measuring the contents of malondialdehyde (MDA) production. Protein expression of HO-1 was determined by Western blotting. Pulmonary neutrophil was counted. Lung tissue myeloperoxidase (MPO) activity as well as plasma levels of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukines 6 and 8 (IL-6, IL-8) were determined by spectrophotography.
      Results: Lung ischemia-reperfusion led to severe lung pathologic morphologic changes and increased pulmonary MDA production, neutrophil count, and MPO activity and reduced arterial oxygen partial pressure (all P < 0.05 IR versus sham), accompanied with a compensatory increase in HO-1 protein and activity. Plasma levels of TNF-α, IL-6, and IL-8 were increased in the IR group (all P < 0.05 versus sham). IPO attenuated or prevented all the above changes, except that it further increased lung HO-1 activity. Treatment with ZnP abolished all the protective effects of postconditioning.
      Conclusion: Postconditioning attenuated pulmonary neutrophil accumulation and activation and lung IRI and reduced systemic inflammatory responses by activating HO-1.
      (Copyright © 2011 Elsevier Inc. All rights reserved.)
    • Accession Number:
      0 (Cytokines)
      0 (Interleukin-6)
      0 (Interleukin-8)
      0 (Tumor Necrosis Factor-alpha)
      EC 1.11.1.7 (Peroxidase)
      EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
      EC 1.14.14.18 (Hmox1 protein, rat)
    • Publication Date:
      Date Created: 20110114 Date Completed: 20110524 Latest Revision: 20161125
    • Publication Date:
      20231215
    • Accession Number:
      10.1016/j.jss.2010.11.902
    • Accession Number:
      21227458