Protective effect of ischemic postconditioning on lung ischemia-reperfusion injury in rats and the role of heme oxygenase-1.
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 chloralhy- drate, 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 micromol/kg/day 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 24 hours prior to 40 minutes clamping of left lung hilum; and HM+S group: HM was administered as in the HM+I/R group without inducing lung I/R. Arterial partial pressure of oxygen (PaO(2)) 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-histochemical technique and for light microscopic examination.


RESULTS
The PaO(2) was significantly lower in all the experimental groups compared with sham group (90 mm Hg +/- 1 mm Hg). However, the values of PaO(2) in IPO (81 mm Hg +/- mm Hg) and HM+I/R (80 mm Hg+/- mm Hg) were higher than that in I/R (63 mm Hg +/- 9 mm Hg) and ZnPPIX+IPO (65 mm Hg +/- 8 mm Hg) groups (P less than 0.01). The protein expression of HO-1 in lung tissue was significantly increased in I/R group compared with S group (P less than 0.01). While the HO-1 protein expression was higher in IPO and HM+I/R groups as compared with I/R group (P less than 0.05, P less than 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 less than 0.01), accompanied by severe lung tissue histological damage, which was attenuated either by IPO or by HM pretreatment (P less than 0.01, IPO or HM+I/R vs. I/R). The protective effect of IPO was abolished by ZnPPIX.


CONCLUSIONS
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.
Xia
Zhong-Yuan
ZY
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China. xiazhongyuan2005@yahoo.com.cn
Gao
Jin
J
Ancharaz
Ameer Kumar
AK
D000818:Animals; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D019194:Ischemic Preconditioning; D008168:Lung / Q000098:blood supply* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D008315:Malondialdehyde; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D010100:Oxygen