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 E2 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.
Key Words
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Article info
Publication history
Published online: July 02, 2010
Received:
May 14,
2010
Identification
Copyright
© 2011 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
