[Protective effects and mechanisms of recombinant human superoxide dismutase in acute lung injury of rats following meconium aspiration].

ABSTRACT

OBJECTIVE: To evaluate the protective effects of recombinant human superoxide dismutase (rhSOD) in acute lung injury (ALI) following meconium aspiration. METHODS: Thirty-two healthy male Sprage-Dawley rats were divided into two groups, 8 were used as control (saline group) by infusing 1 ml/kg saline through endotracheal tube; the other 24 rats were used to establish model of ALI by infusing 1 ml/kg of 20% human newborn meconium suspension through endotracheal tube, and then were randomized to 3 groups (8 each) meconium group with no administration of saline or rhSOD; meconium + saline group by infusing 1 ml/kg saline through endotracheal tube; meconium + rhSOD group by infusing 20 mg/kg rhSOD dissolved in 1 ml/kg saline through endotracheal tube. The rats were killed 24 h after treatment. The measurements included bronchoalveolar lavage fluid (BALF) cell counts, protein, BALF protein/plasma protein (pulmonary permibility index, PPI), lactic dehydrogenase (LDH), pulmonary myeloperoxidase (MPO) and superoxide dismutase (SOD) activity, malonyldialdehyde (MDA) and nitric oxide (NO) level. Lung injury score was also evaluated. RESULTS: Compared with the saline group, the rats in the meconium group had significantly increased BALF cell counts (4.04 +/- 1.01 vs. 0.53 +/- 0.19), protein (2.54 +/- 0.74 vs. 0.67 +/- 0.26), PPI (0.50 +/- 0.18 vs. 0.12 +/- 0.05), LDH (263.50 +/- 97.84 vs. 17.38 +/- 3.58), pulmonary MPO (1.49 +/- 0.22 vs. 0.62 +/- 0.16), MDA (3.30 +/- 0.85 vs. 1.40 +/- 0.35), NO (12.77 +/- 5.00 vs. 4.89 +/- 1.32) and lung injury score (9.88 +/- 2.10 vs. 2.25 +/- 1.04), P < 0.01 for all, whereas pulmonary SOD activity had no statistically significant differences (103.28 +/- 24.53 vs. 94.49 +/- 12.93, P > 0.05). There were no statistically significant differences between meconium + saline group and meconium group (all P > 0.05). Compared with the meconium + saline group, meconium + rhSOD group had decreased BALF cell counts (3.13 +/- 0.77 vs. 4.68 +/- 1.40, P < 0.01), LDH (162.63 +/- 76.90 vs. 273.75 +/- 111.83, P < 0.05), pulmonary MPO activity (1.23 +/- 0.28 vs. 1.54 +/- 0.24, P < 0.05), MDA (2.46 +/- 0.42 vs. 3.50 +/- 0.82, P < 0.01), NO level (9.17 +/- 2.34 vs. 13.04 +/- 4.38, P < 0.05), lung injury score (8.63 +/- 1.30 vs. 10.00 +/- 1.07, P < 0.05) and increased pulmonary SOD activity (134.45 +/- 23.30 vs. 106.79 +/- 17.77, P < 0.05), but there were no statistically significant differences in BALF protein and PPI between these two groups. CONCLUSION: Inflammation and lipid peroxidation might play important roles in the pathogenesis of ALI with meconium aspiration, a single early administration of 20 mg/kg rhSOD intratracheally can reduce lung damage in rats following meconium aspiration.