[Inhibitory effects of melatonin on the expression of phosphorylation p38 mitogen-activated protein kinase during acute lung injury in rats].

Objective To investigate the protective effect of melatonin (MT) on lung tissues during acute lung injury (ALI) in rats and its possible mechanism. Methods Seventy-two Sprague-Dawley (SD) rats were randomly divided into three groups: control group, lipopolysaccharide (LPS) group and MT treatment group. In LPS group and MT treatment group, 1 ml/kg of LPS (200 μg/200 μl) was administered through the airway. In MT group, 10 mg/kg of MT was injected intraperitoneally before and after administration of LPS, and 1 ml/kg of ethanol-normal saline was given in control rats. The rats were sacrificed at 3, 6, 10 hours after administration of LPS, and the lung tissue was obtained for determination of the contents of nitrogen monoxide (NO) and malondialdehyde (MDA), and activity of superoxide dismutase (SOD). In addition, the expression of phosphorylation p38 mitogen-activated protein kinase (p-p38MAPK) in lung tissue was assayed with immunohistochemistry staining. Results Compared with control group, SOD activity (U/mg) decreased significantly in LPS group (3 hours: 73.78±3.62 vs. 112.69±3.26, 6 hours: 66.07±2.31 vs. 117.85±1.96, 10 hours: 55.13±5.26 vs. 118.27±2.16, all P<0.01), but NO (μmol/mg), MDA (nmol/mg) content and the expression of p-p38MAPK [absorbance (A) value] increased obviously (NO: 8.19±0.48 vs. 2.32±0.20 at 3 hours, 11.71±0.27 vs. 2.08±0.15 at 6 hours, 16.53±0.60 vs. 2.76±0.21 at 10 hours; MDA: 11.43±0.68 vs. 2.86±0.21 at 3 hours, 19.63±1.29 vs. 2.85±0.19 at 6 hours, 26.63±2.00 vs. 2.84±0.28 at 10 hours; p-p38MAPK: 0.340±0.020 vs. 0.238±0.019 at 3 hours, 0.410±0.016 vs. 0.218±0.024 at 6 hours, 0.578±0.066 vs. 0.238±0.036 at 10 hours, all P<0.01). The administration of MT mitigated above contents significantly [SOD (U/mg) was 86.02±2.81, 80.87±3.40, 94.46±5.03, NO (μmol/mg) was 3.80±0.28, 5.32±0.22, 7.24±0.52, MDA (nmol/mg) was 8.18±0.84, 7.84±0.78, 6.43±1.06, and p-p38MAPK (A value) was 0.311±0.018, 0.312±0.019, 0.314±0.021 at 3, 6, 10 hours, respectively, P<0.05 or P<0.01]. Conclusion MT possessed protective effect on lung tissues during ALI by its antioxidation effect and inhibition of over-expression of p-p38MAPK. Key words: Melatonin; Antioxidation; p38 mitogen-activated protein kinase; Acute lung injury