Effect of thalidomide in a mouse model of paraquat-induced acute lung injury and the underlying mechanisms / 中华劳动卫生职业病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of thalidomide in a mouse model of paraquat-induced acute lung injury and the mechanisms underlying the properties of thalidomide.</p><p><b>METHODS</b>Male ICR mice were randomly allocated into four groups nomal control group (n = 30), thalidomide control group (n = 30), paraquat poisioning group (n = 30) and thalidomide treatment group (n = 90). Mice were sacrificed at 1d, 3d and 7d after paraquat poisioning. The level of (MDA) malondialdehyde, Superoxidedi-smutase (SOD) and glutathione (GSH) in the lung tissue were measuerd by chemical colorimetry. The expression of Nrf2 mRNA was determined by RT-PCR; Nuclear protein Nrf2 was abserved by Western blotting; Pathological changes of lung tissue were observed under light microscope by HE stain; the lung apoptosis cells were detected by TUNEL.</p><p><b>RESULTS</b>The levels of MDA, SOD and the expressions Nrf2 mRNA and protein Nrf2 in lung tissue were all markedly increased in mice of paraquat poisioning group than those in nomal group at 1 d, 3 d, 7 d. In contrast, the levels of GSH were decreaseel (P<0.05). Compared with paraquat poisioning group, the pulmonary SOD, Nrf2 mRNA and protein were increased and the lung wet dry ratio were all significantly decreased in mice of THD treatment group at 1 d, 3 d, 7 d (P<0.05). THD alleviated the pulmonary damage in the lightmicroscope at 3d after paraquat poisioning. The apoptosis index was markedly decreased in THD treatment groups comparing to paraquat piosioning group (P<0.05).</p><p><b>CONCLUSIONS</b>Lipid peroxide damage was one of the mechanisms of paraquat poisioning, thalidomide could attenuate paraquat-induced acute lung injury and its mechanism may be activating the Nrf2-ARE signaling pathway to protect mouse from Lipid peroxide damage.</p>