Altered plasma proteome during an early phase of peritonitis-induced sepsis

Sepsis is a systemic response to infection commonly found in critically ill patients and is associated with multi-organ failure and high mortality rate. Its pathophysiology and molecular mechanisms are complicated and remain poorly understood. In the present study, we performed a proteomics investigation to characterize early host responses to sepsis as determined by an altered plasma proteome in a porcine model of peritonitis-induced sepsis, which simulated several clinical characteristics of human sepsis syndrome. Haemodynamics, oxygen exchange, inflammatory responses, oxidative and nitrosative stress, and other laboratory parameters were closely monitored. Plasma samples were obtained from seven pigs before and 12 h after the induction of sepsis, and plasma proteins were resolved with two-dimensional gel electrophoresis ( n =7 gels/group; before being compared with during sepsis). The resolved proteins were stained with the SYPRO Ruby fluorescence dye and subjected to quantitative and comparative analyses. From approx. 1500 protein spots visualized in each gel, levels of 36 protein spots were significantly altered in the plasma of animals with sepsis (sepsis/basal ratios or degrees of change ranged from 0.07 to 21.24). Q-TOF (quadrupole–time-of-flight) MS and MS/MS (tandem MS) identified 30 protein forms representing 22 unique proteins whose plasma levels were increased, whereas six forms of five unique proteins were significantly decreased during sepsis. The proteomic results could be related to the clinical features of this animal model, as most of these altered proteins have important roles in inflammatory responses and some of them play roles in oxidative and nitrosative stress. In conclusion, these findings may lead to a better understanding of the pathophysiology and molecular mechanisms underlying the sepsis syndrome. Abbreviations: 2-D, two-dimensional; ACN, acetonitrile; BP, blood pressure; CO, cardiac output; CVP, central venous pressure; DO2, oxygen delivery; DTT, dithiotheitol; FiO2, fraction of inspired oxygen; IEF, isoelectric focusing; IL, interleukin; LPS, lipopolysaccharide; Q-TOF, quadrupole–time-of-flight; MS/MS, tandem MS; NCBI, National Center for Biotechnology Information; NOx, nitrate/nitrite; PAOP, pulmonary artery occlusion pressure; PCO2, partial pressure of carbon dioxide; PEEP, positive end-expiratory pressure; PO2, partial pressure of oxygen; SVR, systemic vascular resistance; TBARS, thiobarbituric acid-reacting substances; TFA, trifluoroacetic acid; TNF-α, tumour necrosis factor-α; VO2, oxygen consumption