| Sepsis is the systemic inflammatory response syndrome (SIRS) induced by infection. It is the common complication of severe trauma, burns, shock, ischemia-reperfusion injury and surgery, and the mortality rate of sepsis is as high as 30-50%. The pathogenesis of sepsis is extremely complicated. Its complexity and nonlinearity lead to the uncertainty of diagnosis, evaluation of prognosis and treatment, which is the main cause of its high mortality. Therefore, to study the biomarkers and find new methods of the diagnosis, prediction, efficacy evaluation of therapies for the guidance of the prevention and treatment, decrease of the morbidity and mortality are of great importance in sepsis.In this study, a sepsis model was made by cecal ligation and puncture (CLP) in rats. The serum levels of inflammatory mediators (TNF-α, IL-1β, IL-6, GM-CSF, HMGB1, MCP-1), BUN, Cr, LDH, ALT, AST, CK and blood routine were detected pre-or post-CLP. The correlation between the changes of these indexes and the outcome of rats were analyzed, the appropriate index set were selected for the assessment of the prognosis of sepsis, with the aims to improve the sensitivity, specificity and accuracy of prognosis evaluation of sepsis. The results were as follows:1. A sepsis model was successfully established by CLP in rats:rats died from 6h post-CLP, the mortality rate was 59%; the serum levels of inflammatory mediators (TNFα, IL-1β, IL-6, GM-CSF, HMGB1) were significantly increased post-CLP; morphological changes were observed in multiple organs at 12h post-CLP, including heart, liver, lung, kidney and brain.2. According to the outcome at 72h post-CLP, the rats were divided into the survival group and non-survival group. In survival group, the serum levels of ALT, AST, HMGB1, IL-6 and MCP-1 were significantly higher at 12 hour post-CLP, compared with pre-CLP (p <0.05 or p<0.01); the white blood cell count, platelet count and serum CK, and IL-1βwere significantly lower at 12 hour post-CLP compared with pre-CLP (p<0.05 or p<0.01). In non-survival group, the body temperature, red blood cell count, hematocrit, serum BUN, ALT, AST, HMGB1, IL-6 and MCP-1 were significantly higher at 12 hour post-CLP compared with pre-CLP (p<0.05 or p<0.01); the white blood count, platelet count, serum CK were significantly lower at 12 hour post-CLP compared with pre-CLP (p<0.05 or p<0.01).3. The serum levels of BUN, Cr, LDH, ALT, CK, IL-6 and MCP-1 were significantly higher in non-survivors compared with survivors (p<0.05 or p<0.01); the platelet count and serum levels of HMGB1 and GM-CSF at 12 hour post-CLP were significantly lower in non-survivors compared with survivors (p<0.05 or p<0.01)4. The body temperature, BUN, Cr, ALT, CK, IL-6 and MCP-1 levels at 12h post-CLP were negatively correlated with rat survival outcome; while the platelet count, HMGB1 and GM-CSF at 12h post-CLP were positively correlated with survival outcome in rats.5. To evaluate the significance of each index and choose the best set of indexes for the prediction of prognosis of sepsis, Logistic regression was used to analyze the above indexes which correlated with sepsis prognosis and it was found that when BUN, Cr, IL-6, GM-CSF were selected into the equation, the predict sensitivity (86.2%), specificity (83.3%) and accuracy (84.7%) of prediction reached the maximum. The regression equation was as follows: Logit P=-8.367+1.124 BUN+1.134Cr+0.003 IL-6-0.249GM-CSF P is the ratio of the probability of non-survival and survival and Logit P is the natural logarithm of P.In summary, in this study a optimal index set was selected for the prediction of prognosis in sepsis by using a CLP model in rats and a prediction model with the best index set was established. It was shown by the prediction model that a poor prognosis in sepsis was associated with a high serum level of BUN, Cr and IL-6 and a low serum level of GM-CSF. These results provided new experimental evidences and research ideas for the prognosis prediction and efficacy evaluation of therapies in sepsis.
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