Proteomic analysis of lung injuries induced by paraquat in mice / 中华急诊医学杂志

ABSTRACT

Objective:To explore the molecular mechanism of paraquat (PQ)-induced lung injuries.Methods:Male C57BL/6 mice aged 6 to 8 weeks were randomly divided into four groups. Mice in the experimental groups (three groups, nine rats in each group) were intraperitoneally injected with 40 mg/kg PQ to establish an infection model, and mice in the control group ( n=9) were intraperitoneally injected with the same dose of saline. Mice were sacrificed at day 2, 7 and 14 after PQ administration. Pathological changes of lung tissues from mice model were observed by Hematoxylin-eosin staining. The expression of different proteins in the lung tissues at different time points were detected and identified by tandem mass spectrometry tag technology (TMT), and the functional analysis was performed. Results:Compared with the control group, there were 91 (69 up and 22 down), 160 (103 up and 57 down) and 78 (45 up and 33 down) proteins in the PQ-2 d, 7 d, and 14 d groups, respectively, and there was significant difference of protein expression . The subcellular localization analysis showed that compared with the control group, the differentially-expressed proteins in the PQ-2 d and -7 d groups were mainly distributed in the extracellular space, while in the PQ-14 d group were mainly distributed in the nuclear. GO analysis showed that compared with the control group, the differentially-expressed proteins in the PQ-2 d and PQ-7 d groups were mainly involved in humoral immunity and coagulation-related reactions, while in the PQ-14 d group were mainly involved in chemotactic and regulatory responses such as neutrophil aggregation. The KEGG signaling pathway analysis showed that the complement and coagulation cascades was the most important pathway in the PQ-2d and PQ-7 d groups, while metabolism of xenobiotics by cytochrome P450 was the most important pathway in the PQ-14 d group.Conclusions:It is the first time that TMT was used to analyze PQ-induced lung injuries in mice model at different time points. This study demonstrates the molecular mechanism of PQ-induced lung injuries at protein levels, and elucidates that humoral immunity and complement-coagulation pathways charge the main role of PQ-induced lung injuries. This study may provide an important theoretical basis for further research and clinical treatment.