Expression and role of mitogen activated protein kinases signaling pathway in lung injury induced by phosgene / 中华劳动卫生职业病杂志

ABSTRACT

<p><b>OBJECTIVE</b>This study aimed to investigate the expression and role of the mitogen activated protein kinases (ERK1/2, P38, JNK) in phosgene induced lung injury in rats in vivo.</p><p><b>METHOD</b>30 male wistar rats were randomized into the group as follows, Gas inhalation control group, Phosgene inhalation group, and the following groups of the inhibitors of MAPK, involving SP600125, PD98059 and SB203580, 6 animals in each group, we copy the model of phosgene-induced lung injury, used the directional flow-inhalation device, the air control group inhaled the air, and the intervention groups were given PD98059 (intraperitoneal injection), SB203580 (hypodermic injection), SP600125 (intravenous) respectively before the inhalation of phosgene. The locations and quantities of three subfamilies of MAPKs (ERK1/2, P38, JNK) and p-MAPKs (p-ERK1/2, p-P38, p-JNK) were analyzed by immunohistochemistry and Western Blot analysis respectively; The histopathological changes of lung tissues, the number of neutrophil cells and the W/D were examined.</p><p><b>RESULT</b>There were rare p-ERK1/2, p-P38 and p-JNK positive expression in alveolar and airway epithelial cells in control group. while the positive cells increased strikingly in phosgene inhalation groups, these cells involved in this process mainly included alveolar epithelial cells, air way epithelial cells, pleural mesothelial cells, infiltrative inflammatory cells, interstitium fibrocytes. After the intervention of the specific inhibitor, the positive cells decreased. As Western Blot analysis show, Protein quantities of p-P38 and p-JNK were higher in phosgene inhalation groups than those in control group, and the differences were significant (P < 0.05). Protein quantities of p-ERK1/2, p-P38 and p-JNK were lower in intervention groups than phosgene inhalation group, and the differences were significant (P < 0.05, P < 0.01). The lung injury in phosgene inhalation groups was more severer compared with the control group, the typical pathological characters of acute lung injury were discovered, the increase of the number of neutrophil cells and W/D. After the intervention of the specific inhibitor SP600125 and SB203580, the number of neutrophil cells and W/D reduced, and the differences were significant (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Phosgene inhalation may activate the MAPK signaling pathway, and the expression of the phosphorylation of MAPKs increased, especially the P38 ang JNK. The results may contribute to the lung injury induced by phosgene.</p>