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The emergence of ischaemic post-conditioning (IPO) provides a potential method for experimentally and clinically attenuating various types of organ injuries. There has been little work, however, examining its effects in the setting of lung ischaemia reperfusion (IR). The stress protein, haeme oxygenase-1 (HO-1), has been found to exert a potent, protective role in a variety of lung injury models. In this study, we hypothesised that the induction of HO-1 by IPO plays a protective role against the deleterious effects of IR in the lung.Anaesthetised 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 IR group (40 min of left-lung ischaemia and 105 min of reperfusion), the IPO group (three successive cycles of 30-s reperfusion per 30-s occlusion before restoring full perfusion) and the ZnPPIX+IPO group (ZnPPIX, an inhibitor of HO-1, was injected intra-peritoneally at 20 mg kg(-1) 24h 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 histological changes. The extent of lipid peroxidation was determined by measuring plasma levels of malondialdehyde (MDA) production. Expression of HO-1 was determined by immunohistochemistry.Lung IR resulted in a significant reduction of PaO(2) (data in IR, P0.05 vs. data in sham) and increase of lung wet-to-dry weight ratio, accompanied with increased MDA production and severe lung pathological morphological changes as well as a compensatory increase in HO-1 protein expression, as compared with sham (All P0.05). IPO markedly attenuated all the above pathological changes seen in the IR group and further increased HO-1 expression. Treatment with ZnPPIX abolished all the protective effects of post-conditioning.It may be concluded that IPO protects IR-induced lung injury via induction of HO-1.

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.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.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.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.