Ischaemic post-conditioning protects lung from ischaemia-reperfusion injury by up-regulation of haeme oxygenase-1.
OBJECTIVE
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.


METHODS
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.


RESULTS
Lung IR resulted in a significant reduction of PaO(2) (data in IR, P<0.05 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 P<0.05). 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.


CONCLUSIONS
It may be concluded that IPO protects IR-induced lung injury via induction of HO-1.
Xia
Zhong-yuan
ZY
Anesthesiology Research Laboratory, Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, PR China.
Gao
Jin
J
Ancharaz
Ameer Kumar
AK
Liu
Ke-xuan
KX
Xia
Zhengyuan
Z
Luo
Tao
T
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000098:blood supply*; D011524:Protoporphyrins / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion / Q000379:methods*; D015427:Reperfusion Injury / Q000517:prevention & control*; D015854:Up-Regulation
D004791:Enzyme Inhibitors; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D051547:Heme Oxygenase-1