RESUMEN
OBJECTIVE: The paper is an attentative effort to evaluate the reaction and mechanism of estrogen on pregnant rabbits with acute lung injury caused by hemorrhagic shock. METHODS: Sixty pregnant New Zealand white rabbits were randomly divided into 6 groups, with 10 rabbits in each group, namely normal control group (NG group, with anesthesia only), estrogen group (E(2)G group, with additional estrogen injection at 60 min) and the other four hemorrhagic shock groups underwent hemorrhagic shock (i.e. E(2)SG, FSG, SBSG, E(2)SBSG group; mean blood pressure- 40 mmHg (1 mmHg = 0.133 kPa) by phlebotomy for 15 min. After maintenance of the pressure for 45 min, the rabbits were treated with E(2) (0.37 mg/kg), fructose injection (5%, 2 ml/kg), the p38 mitogen-activated protein kinases (p38MAPK) inhibitor SB-203580 (2 mg/kg) or E(2) plus SB-203580. Tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) were measured at different time points (0 min, 60 min, 80 min and 260 min), lung tissue methane dicarboxylic aldehyde (MDA) level, lung tissue myeloperoxidase (MOP), superoxide dismutase (SOD) activity, lung tissue dry weight/wet weight (DW/WW) value were measured after the experiment was finished, pulmonary pathology of the rabbits was observed. RESULT: (1) Serum TNF-α level of NG group and E(2)SG group were not significantly different compared with the other four groups at the 0 min and 60 min. At 80 min and 260 min of experiment, serum TNF-α level of all the four shock groups were increased, E(2)SG group [(172.4 ± 16.0) and (216.7 ± 18.6) ng/L], FSG group [(171.6 ± 9.1) and (263.9 ± 7.8) ng/L], SBSG group [(172.8 ± 7.2) and (300.6 ± 4.8) ng/L], E(2)SBSG group [(167.9 ± 4.8 ) and (261.8 ± 9.6) ng/L], and significantly higher than NG group and E(2)G group, separately (P < 0.05). (2) Serum IL-6 level of NG group and E(2)SG group were not significantly different compared with the other four groups at the 0 min, 60 min and 80 min. At 260 min, the serum IL-6 level [(98.3 ± 0.9) and (110.4 ± 1.8) ng/L; (120.9 ± 2.3) and (109.8 ± 2.6) ng/L] of the four shock groups (E(2)SG, FSG, SBSG, E(2)SBSG group) were significantly higher than NG group and E(2)G group (P < 0.05). (3) Lung tissue MDA level [(2.20 ± 0.12), (2.57 ± 0.11), (3.17 ± 0.08), (2.75 ± 1.09) nmol/mg] and MPO activity [(4.45 ± 0.25), (6.65 ± 0.56), (9.55 ± 0.30), (6.78 ± 0.11) U/mg] of the four shock groups (E(2)SG, FSG, SBSG, E(2)SBSG group) were higher than NG group and E(2)G group (P < 0.05). (4) Lung tissue SOD activity [(51.8 ± 1.8), (40.2 ± 1.5), (30.0 ± 1.7), (41.2 ± 2.0) U/mg] was significantly higher in the four shock groups (E(2)SG, FSG, SBSG, E(2)SBSG group) compared with NG group and E(2)G group (P < 0.05). (5) Lung tissue DW/WW value (0.143 ± 0.008, 0.127 ± 0.008, 0.109 ± 0.006, 0.125 ± 0.008) was significantly lower in the four shock groups (E(2)SG, FSG, SBSG, E(2)SBSG group) compared with NG group and E(2)G group (P < 0.05). (6) Lung tissue of the rabbits in NG group and E(2)G group is basically normal without obvious pathology changes. Lung tissue pathological damage of rabbits was observed in the four shock groups, and the pathological damage of rabbits in SBSG group was most serious. CONCLUSION: Estrogen can reduce acute lung injury of pregnant rabbits with hemorrhagic shock, the p38MAPK pathway plays a critical role in mediating the salutary effects of E(2) on shock-induced acute lung injury.