[The role of heme oxygenase-1 in the protection of chronic intermittent hypoxia-induced lung injury in vivo].

OBJECTIVE

To investigate the effect of chronic intermittent hypoxia (CIH) on inflammatory and pathological changes of the lung in an animal model as well as the protective effect of heme oxygenase-1 in this process.

METHODS

Twenty-four Male Sprague-Dawley rats were randomly divided into 4 groups: intermittent normoxia (IN) group, CIH group, IN+hemin injection (hemin) group and CIH+hemin injection (CIH+hemin) group. The CIH profiling was repetitive 4 min 10% O₂and 2 min 21% O₂for 8 hours per day for 6 weeks. Animals exposed to IN were kept in an identical chamber receiving intermittent air at the same flow rate. Hemin was intraperitoneally injected (4 mg/kg) to induced HO-1 expression, and other 2 groups only received an injection of same amount of saline. Western blot was utilized to detect the pulmonary HO-1 expression levels and ELISA was used to examine the pulmonary cytokine levels. H&E staining was used to investigate pathological changes of the lung.

RESULTS

CIH significantly induced HO-1 expression in the lung and hemin induced a synergistic increase of HO-1 expression. CIH exposure significantly increased pulmonary inflammatory cytokines levels, TNF-α [(2.20 ± 0.10) vs (1.80 ± 0.08) ng/ml], IL-6 [(0.87 ± 0.05) vs (0.52 ± 0.05) ng/ml], CINC-1 [(66 ± 6) vs (39 ± 5) pg/ml] and MCP-1 [(2.20 ± 0.09) vs (1.40 ± 0.10) ng/ml], accelerated cell apoptosis and induced pathological changes of the lung, while hemin could inhibit the elevation of cytokines [(TNF-α:(1.60 ± 0.20) ng/ml, IL-6: (0.60 ± 0.07) ng/ml, CINC-1: (45 ± 6) pg/ml, MCP-1: (1.80 ± 0.10) ng/ml, all P<0.05] and cell apoptosis, as well as reversing the structural injury of the lung under CIH condition.

CONCLUSIONS

CIH leads to inflammatory stress, cell apoptosis and pathological changes within the lung, while HO-1 could inhibit inflammation and apoptosis, thereby reversing the pulmonary injury.