Objective
To investigate the effect of ischemic postconditioning (IPO) on acute lung ischemia-reperfusion (I/R) injury and the protein expression of
haeme oxygenase-
1 (HO-
1), a cytoprotective defense against oxidative injury.
Methods
After being anesthetized with chloralhydrate, forty-eight healthy SD rats were randomly divided into 6 groups (8 in each): sham operation group (S group); I/R group: left lung hilum was clamped for 40 minutes followed by 105 minutes of reperfusion; IPO group: left lung hilum was clamped for 40 minutes and postconditioned by 3 cycles of 30 seconds of reperfusion and 30 seconds of reocclusion; Hemin (HM)+ I/R group: hemin, an inducer of HO-1 was injected intraperitoneally at 40 μmol·kg"12;1 ·day"12;1 for two consecutive days prior to 40 minutes clamping of left lung hilum; ZnPPIX+IPO group: zinc protoporphyrin IX, an inhibitor of HO-1 was injected intraperitoneally at 20 mg·kg"12;1 24 hours prior to 40 minutes clamping of left lung hilum; and HM+S group: H M was administered as in the HM+I/R group without inducing lung I/R. Arterial partial pressure of oxygen (PaO2) and malondialdehyde (MDA) content in serum were assessed. The left lung was removed for determination of wet/dry lung weight ratio and expression of HO-1 protein by immuno-his-tochemical technique and for light microscopic examination.
Results
The PaO2 was significantly lower in all the experimental groups compared with sham group (90 mm Hg 1; 11 mm Hg). However, the values of PaO2 in IPO (81 mm Hg 1; 7 mm Hg) and HM+I/R (80 mm Hg 1; 9 mm Hg) were higher than that in I/R (63 mm Hg 1; 9 mm Hg) and ZnPPIX+IPO (65 mm Hg 1;8 mm Hg) groups (P<0.01). The protein expression of HO-1 in lung tissue was significantly increased in I/R group compared with S group (P<0.01). While the HO-1 protein expression was higher in IPO and HM+I/R groups as compared with I/R group (P<0.05, P<0.01). The lung wet/dry (W/D) weight ratio and MDA content in serum were significantly increased in I/R group as compared with S or HM+S groups (P<0.01), accompanied by severe lung tissue histological damage, which was attenuated either by IPO or by HM pretreatment (P<0.01, IPO or HM+I/R vs. I/R). The protective effect of IPO was abolished by ZnPPIX.
Conclusion
Ischemic postconditioning can attenuate the lung ischemia-reperfusion injury through upregulating the protein expression of HO-1 that leads to reduced post-ischemic oxidative damage.
