Background Treatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmon...Background Treatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmonary inflammation and lung injury during acute endotoxemia. Methods Thirty-two male Sprague-Dawley rats were randomly assigned to four groups： vehicle ＋ saline group, melatonin ＋ saline group, vehicle ＋ lipopolysaccharide group, melatonin ＋ lipopolysaccharide group. The rats were treated with melatonin （10 mg/kg, intraperitoneal injection （i.p.）） or vehicle （1% ethanol saline）, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, intravenous injection）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Blood gas analysis was carried out. Optical microscopy was performed to examine pathological changes in lungs and lung injury score was assessed. Wet/dry ratios （W/D）, myeloperoxidase activity, malondialdehyde concentrations and tumor necrosis factor-alpha （TNF-α） and interleukin-10 （IL-10） levels in lungs were measured. The pulmonary expression of nuclear factor-kappa B （NF-κB） p65 was evaluated by Western blotting. Results PaO2 in the vehicle ＋ lipopolysaccharide group decreased compared with that in the vehicle ＋ saline group. This decrease was significantly reduced in the melatonin ＋ lipopolysaccharide group. The lung tissues from the saline ＋ lipopolysaccharide group were significantly damaged, which were less pronounced in the melatonin ＋ lipopolysaccharide group. The W/D ratio increased significantly in the vehicle ＋ lipopolysaccharide group （6.1±0.18） as compared with that in the vehicle ＋ saline group （3.61±0.3） （P 〈0.01）, which was significantly reduced in the melatonin ＋ lipopolysaccharide group （4.8±0.25） （P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the vehicle ＋ lipopolysaccharide group compared with that in the vehicle ＋ saline group, which was reduced in the melatonin ＋ lipopolysaccharide group. The TNF-a level of pulmonary tissue increased significantly in the vehicle ＋ lipopolysaccharide group （（8.7±0.91） pg/mg protein） compared with that in the vehicle ＋ saline group （（4.3±0.62） pg/mg protein, P 〈0.01）. However, the increase of TNF-a level of pulmonary tissue was significantly reduced in the melatonin ＋ lipopolysaccharide group （（5.9±0.56） pg/mg protein, P 〈0.01）. Pulmonary IL-10 levels were elevated markedly in the vehicle ＋ lipopolysaccharide group in contrast to that in the vehicle ＋ saline group, whereas the elevation was augmented in the melatonin ＋ lipopolysaccharide group. The nuclear localization of p65 increased markedly in the vehicle ＋ lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the melatonin ＋ lipopolysaccharide group. Conclusion Melatonin reduces acute lung injury in endotoxemic rats by attenuating pulmonary inflammation and inhibiting NF-κB activation.展开更多
Background Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung inju...Background Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung injury during acute endotoxaemia.Methods A total of 32 male Sprague-Dawley rats were randomly assigned to four groups： saline group, erythropoietin＋saline group, saline＋lipopolysaccharide group and erythropoietin＋lipopolysaccharide group. Rats were treated with erythropoietin （3000 U/kg, i.p.） or saline, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, i.v.）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Wet/dry （W/D） ratios, myeloperoxidase activity, malondialdehyde concentrations and tumour necrosis factor-alpha （TNF-α） as well as interleukin 1 beta （IL-1β） levels in lungs were measured. The pulmonary expression of nuclear factor kappaB （NF-κB） p65 was evaluated by Western blotting. Differences between the different groups were analysed by one-way analysis of variance （ANOVA）.Results The lung tissues from the saline＋lipopolysaccharide group were significantly damaged, which were less pronounced in the erythropoietin＋lipopolysaccharide group. The W/D ratio increased significantly in the saline＋lipopolysaccharide group （5.75±0.22） as compared with the saline group （3.85±0.20） （P 〈0.01）, which was significantly reduced in the erythropoietin＋lipopolysaccharide group （4.50±0.35） （P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the saline＋lipopolysaccharide group compared with the saline group, which was reduced in the erythropoietin ＋ lipopolysaccharide group. The TNF-α level of pulmonary tissue increased significantly in the saline＋lipopolysaccharide group （（9.80±0.82） pg/mg protein） compared with the saline group （（4.20=L-0.42） pg/mg protein, P 〈0.01）. However, the increase of TNF-α level of pulmonary tissue was significantly reduced in the erythropoietin＋lipopolysaccharide group （（6.50±0.66） pg/mg protein, P 〈0.01）. Similarly, pulmonary IL-1β levels were elevated markedly in the saline＋lipopolysaccharide group in contrast to the saline group, whereas the elevation was much less in the erythropoietin＋lipopolysaccharide group. The nuclear localization of p65 increased markedly in the saline＋lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the erythropoietin＋lipopolysacchadde group.Conclusion Erythropoietin attenuates pulmonary inflammation and suppresses TNF-α and IL-1β overproduction during acute endotoxaemia, which is partially mediated by inhibition of NF-KB.展开更多
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 30571787）.
文摘Background Treatment with melatonin significantly reduces lung injury induced by bleomycin, paraquat and ischemia reperfusion. In the present study, we investigated the possible protective roles of melatonin in pulmonary inflammation and lung injury during acute endotoxemia. Methods Thirty-two male Sprague-Dawley rats were randomly assigned to four groups： vehicle ＋ saline group, melatonin ＋ saline group, vehicle ＋ lipopolysaccharide group, melatonin ＋ lipopolysaccharide group. The rats were treated with melatonin （10 mg/kg, intraperitoneal injection （i.p.）） or vehicle （1% ethanol saline）, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, intravenous injection）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Blood gas analysis was carried out. Optical microscopy was performed to examine pathological changes in lungs and lung injury score was assessed. Wet/dry ratios （W/D）, myeloperoxidase activity, malondialdehyde concentrations and tumor necrosis factor-alpha （TNF-α） and interleukin-10 （IL-10） levels in lungs were measured. The pulmonary expression of nuclear factor-kappa B （NF-κB） p65 was evaluated by Western blotting. Results PaO2 in the vehicle ＋ lipopolysaccharide group decreased compared with that in the vehicle ＋ saline group. This decrease was significantly reduced in the melatonin ＋ lipopolysaccharide group. The lung tissues from the saline ＋ lipopolysaccharide group were significantly damaged, which were less pronounced in the melatonin ＋ lipopolysaccharide group. The W/D ratio increased significantly in the vehicle ＋ lipopolysaccharide group （6.1±0.18） as compared with that in the vehicle ＋ saline group （3.61±0.3） （P 〈0.01）, which was significantly reduced in the melatonin ＋ lipopolysaccharide group （4.8±0.25） （P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the vehicle ＋ lipopolysaccharide group compared with that in the vehicle ＋ saline group, which was reduced in the melatonin ＋ lipopolysaccharide group. The TNF-a level of pulmonary tissue increased significantly in the vehicle ＋ lipopolysaccharide group （（8.7±0.91） pg/mg protein） compared with that in the vehicle ＋ saline group （（4.3±0.62） pg/mg protein, P 〈0.01）. However, the increase of TNF-a level of pulmonary tissue was significantly reduced in the melatonin ＋ lipopolysaccharide group （（5.9±0.56） pg/mg protein, P 〈0.01）. Pulmonary IL-10 levels were elevated markedly in the vehicle ＋ lipopolysaccharide group in contrast to that in the vehicle ＋ saline group, whereas the elevation was augmented in the melatonin ＋ lipopolysaccharide group. The nuclear localization of p65 increased markedly in the vehicle ＋ lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the melatonin ＋ lipopolysaccharide group. Conclusion Melatonin reduces acute lung injury in endotoxemic rats by attenuating pulmonary inflammation and inhibiting NF-κB activation.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 30571787）.
文摘Background Erythropoietin elicits protective effects in lung tissue injury induced by ischaemic reperfusion and hyperoxia. We investigated the protective roles of erythropoietin in pulmonary inflammation and lung injury during acute endotoxaemia.Methods A total of 32 male Sprague-Dawley rats were randomly assigned to four groups： saline group, erythropoietin＋saline group, saline＋lipopolysaccharide group and erythropoietin＋lipopolysaccharide group. Rats were treated with erythropoietin （3000 U/kg, i.p.） or saline, 30 minutes prior to lipopolysaccharide administration （6 mg/kg, i.v.）. Four hours after lipopolysaccharide injection, samples of pulmonary tissue were collected. Optical microscopy was performed to examine pathological changes in lungs. Wet/dry （W/D） ratios, myeloperoxidase activity, malondialdehyde concentrations and tumour necrosis factor-alpha （TNF-α） as well as interleukin 1 beta （IL-1β） levels in lungs were measured. The pulmonary expression of nuclear factor kappaB （NF-κB） p65 was evaluated by Western blotting. Differences between the different groups were analysed by one-way analysis of variance （ANOVA）.Results The lung tissues from the saline＋lipopolysaccharide group were significantly damaged, which were less pronounced in the erythropoietin＋lipopolysaccharide group. The W/D ratio increased significantly in the saline＋lipopolysaccharide group （5.75±0.22） as compared with the saline group （3.85±0.20） （P 〈0.01）, which was significantly reduced in the erythropoietin＋lipopolysaccharide group （4.50±0.35） （P 〈0.01）. Myeloperoxidase activity and malondialdehyde levels increased significantly in the saline＋lipopolysaccharide group compared with the saline group, which was reduced in the erythropoietin ＋ lipopolysaccharide group. The TNF-α level of pulmonary tissue increased significantly in the saline＋lipopolysaccharide group （（9.80±0.82） pg/mg protein） compared with the saline group （（4.20=L-0.42） pg/mg protein, P 〈0.01）. However, the increase of TNF-α level of pulmonary tissue was significantly reduced in the erythropoietin＋lipopolysaccharide group （（6.50±0.66） pg/mg protein, P 〈0.01）. Similarly, pulmonary IL-1β levels were elevated markedly in the saline＋lipopolysaccharide group in contrast to the saline group, whereas the elevation was much less in the erythropoietin＋lipopolysaccharide group. The nuclear localization of p65 increased markedly in the saline＋lipopolysaccharide group and this enhancement of nuclear p65 expression was much less in the erythropoietin＋lipopolysacchadde group.Conclusion Erythropoietin attenuates pulmonary inflammation and suppresses TNF-α and IL-1β overproduction during acute endotoxaemia, which is partially mediated by inhibition of NF-KB.
