Expressions of nuclear factor-erythroid 2-related factor and heme oxygenase-1 in acute pulmonary injury induced by seawater and freshwater drowning

Abstract

Objective To observe the expression levels of nuclear factor-erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in acute pulmonary injury induced by seawater and freshwater drowning. Methods Eighteen New Zealand rabbits were randomly assigned to the 3 groups: the seawater group, the freshwater group and the control group, each consisting of 6 animals. In the seawater group, seawater was injected into the trachea at a dosage of 3ml/kg, while in the freshwater group, freshwater was injected into the trachea at a dosage of18ml/kg. Upon establishment of the animal model, arterial oxygen partial pressure levels were detected at 0h, 0.5h, 1h, 3h and 6h, after establishment of the model. The animals were sacrificed and lung tissue samples were taken for the detection of lung wet/dry weight (W/D) ratio, pulmonary permeability data and tumor necrosis factor-α (TNF-α), interleukin-1β(IL-1β), IL-6 and IL-10 levels in bronchoalveolar lavage fluid (BALF) . At the same time, changes in the histopathology of the pulmonary tissue were also detected. Lung specimens were evaluated by hematoxylin-eosin staining. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were also assayed, and caspase-3, Nrf2 and HO-1 expression levels were measured by quantitative real-time PCR and Western blot. Results Oxygenation levels of the seawater and freshwater groups were dramatically decreased, as compared with those of the control group(P<0.05). The W/D ratio and pulmonary permeability data of the seawater and freshwater groups were significantly increased, as compared with those of the control group. Furthermore, the values of TNF-α, IL-6, IL-1β and IL-10 were also significantly increased in BALF as compared with those of the control group(P<0.05). TNF-α values of the seawater and freshwater groups were respectively (121.8±22.7) pg/ml and (113.5±23.0) pg/ml, while that of the control group was (82.8±16.5) pg/ml. IL-1β values of the seawater and freshwater groups were respectively (76.4±15.5) pg/ml and (62.2±12.8) pg/ml, while that of the control group was (32.2±7.4) pg/ml. IL-6 levels of the seawater and freshwater groups were respectively (34.1±7.6) pg/ml and (35.0±7.4) pg/ml, while that of the control group was (16.5±3.8) pg/ml. IL-10 levels of the seawater and freshwater groups were respectively (22.1±3.9) pg/ml and (19.0±2.8) pg/ml, while that of the control group was (13.4±2.8) pg/ml. Pulmonary lesion of the seawater and freshwater groups were obviously severer, as compared with that of the control group. MDA and SOD levels of the seawater and freshwater groups were obviously higher than that of the control group(P<0.05). Caspase-3 levels of the seawater and freshwater groups were higher than that of the control group(P<0.05). Nrf2, HO-1mRNA and protein levels of the seawater and freshwater groups in the pulmonary tissue were also higher than those of the control group(P<0.05). No statistic significance could be seen, when comparisons were made between the seawater and freshwater groups (P<0.05). Conclusions pulmonary lesion induced by seawater and freshwater drowning was identical, oxidative stress lesion and cell necrosis were present in both cases, and Nrf2/HO-1 pathway might be involved in the protection of pulmonary tissue following seawater and freshwater drowning. Key words: Drowning; Pulmonary lesion; Nuclear factor-erythroid 2; Heme oxygenase-1