title: Heme oxygenase-1 mediates the protective effects of ischemic preconditioning on mitigating lung injury induced by lower limb ischemia-reperfusion in rats.
abstract: BACKGROUND
  Lower limb ischemia-reperfusion (I/R) imposes oxidative stress, elicits inflammatory response, and subsequently induces acute lung injury. Ischemic preconditioning (IP), a process of transient I/R, mitigates the acute lung injury induced by I/R. We sought to elucidate whether the protective effects of IP involve heme oxygenase-1 (HO-1).
  
  
  METHODS
  Adult male rats were randomized to receive I/R, I/R plus IP, I/R plus IP plus the HO-1 inhibitor tin protoporphyrin (SnPP) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquet high around each thigh for 3 h followed by reperfusion for 3 h. To achieve IP, three cycles of bilateral lower limb I/R (i.e., ischemia for 10 min followed by reperfusion for 10 min) were performed. IP was performed immediately before I/R. After sacrifice, degree of lung injury was determined.
  
  
  RESULTS
  Histologic findings, together with assays of leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity) and lung water content (wet/dry weight ratio), confirmed that I/R induced acute lung injury. I/R also caused significant inflammatory response (increases in chemokine, cytokine, and prostaglandin E(2) concentrations), imposed significant oxidative stress (increases in nitric oxide and malondialdehyde concentrations), and up-regulated HO-1 expression in lung tissues. IP significantly enhanced HO-1 up-regulation and, in turn, mitigated oxidative stress, inflammatory response, and acute lung injury induced by I/R. In addition, the protective effects of IP were counteracted by SnPP.
  
  
  CONCLUSIONS
  The protective effects of IP on mitigating acute lung injury induced by lower limb I/R are mediated by HO-1.
authors.affiliation: Department of Anesthesiology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan.
authors.forename: Tsui-Chin
authors.initials: TC
authors.lastname: Peng
authors.forename: Woan-Ching
authors.initials: WC
authors.lastname: Jan
authors.forename: Pei-Shan
authors.initials: PS
authors.lastname: Tsai
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Huang
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D019194:Ischemic Preconditioning; D007962:Leukocytes / Q000473:pathology; D035002:Lower Extremity / Q000098:blood supply*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology; D023421:Models, Animal; D018384:Oxidative Stress / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology
chemical_list: D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D011524:Protoporphyrins; D008315:Malondialdehyde; C032628:tin protoporphyrin IX; D009195:Peroxidase; D051547:Heme Oxygenase-1