[Study on activation of mitogen-activated protein kinase pathway in lung tissue of rats with smoke inhalation injury].
OBJECTIVE
To investigate the activation of mitogen-activated protein kinase (MAPK) pathway and the expression of inflammatory cytokine in lung tissue of rats with smoke inhalation injury, and to explore the injury mechanism.


METHODS
The model of smoke inhalation injury in airtight cabin was established. Thirty-six SD rats were randomly divided into normal control group (n = 6, NC group) and inhalation injury group (n = 30, II group). The rats in II group were observed at 1, 6, 24, 72 post injury hour (PIH) and 7 post injury day (PID). The pathological changes in lung tissue were observed by optical microscope. The contents of TNF-alpha, MIP-2, IL-1beta in lung tissue homogenate were examined. The level of p38MAPK, JNK, ERK1/2 and their phosphorylation in lung tissue were measured by Western blotting. The contents of TNF-alpha, MIP-2, and IL-1beta and granulocytes counts in BALF (bronchoalveolar lavage fluid) were detected by ELISA.


RESULTS
Pathological change of smoke inhalation was similar to acute lung injury. The contents of TNF-alpha and IL-1beta of lung tissue and BALF in II group at 1 PIH were higher than those in NC group (P < 0.01). The levels of MIP-2 of lung tissue in II group at each time point were similar to that in NC group (P > 0.05), while that of BALF in II group at 1 PIH were obviously higher than that in NC group (P < 0.01). Compared with those in NC group, the levels of p38MAPK, JNK, ERK1/2 in II group at each time point were similar, and their phosphorylation levels increased with different degree. Compared with that in NC group [(0.61 +/- 0.09) x 10(6) cells/L], the total number of granulocytes in II group was significantly decreased at 1PIH [(0.36 +/- 0.08) x 10(6) cells/L], increased on 7PID [(1.71 +/- 0.67) x 10(6) cells/L, P < 0.05]. The number of neutrophils in II group during 6PIH approximately 7 PID were more than that in NC group. The number of lymphocyte in II group at 1PIH less than that in NC group (P < 0.05), which increased gradually during 6 PIH approximately 7PID. There were no obvious difference in number of lymphocyte between two groups (P > 0.05).


CONCLUSIONS
The obvious inflammatory response in lung tissue can be induced by the poisonous gas released from the combustion of nonmetal materials in airtight cabin, and activate the expression of kinases in MAPK pathway, which may be one of mechanisms for lung injury induced by poisonous gas.
An
Hui
H
Department of Hygienic Toxicology, Preventive Medical College, the Third Military Medical University, Chongqing 400038, PR China.
Sun
Lei
L
Zhou
Yan-hong
YH
Cao
Jia
J
D000818:Animals; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D055370:Lung Injury / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015208:Smoke Inhalation Injury / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases