The Secretome Deregulations in a Rat Model of Endotoxemic Shock

内毒血症性休克大鼠模型中的分泌组失调

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作者:A Blangy-Letheule, A Persello, S Michelland, V Cunin, F Souab, V Aillerie, J Dhot, A Erraud, J Montnach, M Seve, S Bourgoin-Voillard, B Rozec, M De Waard, B Lauzier

Aims

To identify relevant deregulated proteins (DEP) in the secretome of a rat endotoxemic shock model.

Conclusion

This study proposes an approach to identify relevant DEP in septic shock and brings new insights into the understanding of the secretome adaptations upon sepsis.

Methods

Endotoxemic shock was induced in rats by intravenous injection of lipopolysaccharides (LPS, S. enterica typhi, 0.5 mg/kg) and compared to controls (Ringer Lactate, iv). Under isoflurane anesthesia, carotid cannulation allowed mean arterial blood pressure (MAP) and heart rate (HR) monitoring and blood sampling at different time points (T0 and T50 or T0 and T90, with EDTA and protease inhibitor). Samples were prepared for large-scale tandem mass spectrometry (MS-MS) based on a label-free quantification to allow identification of the proteins deregulated upon endotoxemic conditions. A Gene Ontology (GO) analysis defined several clusters of biological processes (BP) in which the DEP are involved.

Results

Ninety minutes after shock induction, the LPS group presents a reduction in MAP (-45%, p < 0.05) and increased lactate levels (+27.5%, p < 0.05) compared to the control group. Proteomic analyses revealed 10 and 33 DEP in the LPS group, respectively, at 50 and 90 minutes after LPS injection. At these time points, GO-BP showed alterations in pathways involved in oxidative stress response and coagulation.

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