| Burn injury leads to a prolonged inflammatory response in the body. Moreover, severe burn injuries are always associated with bacterial infections which cause more persistent inflammatory response, resulting in prolonged hyper-metabolism and hyper-catabolism on systemic level. Despite significant advances in patient care, morbidity and mortality remain high in those patients. The difficulty in developing new and more effective medications is due, in part, to our incomplete understanding of the underlying pathophysiology of the disease. Liver, the main organ regulating both the inflammation and metabolism plays a key role in responding to external injuries. Thus, analyzing the responses in liver to burn, infection and "double hits" injury from global perspective as well as in a timely manner may offer a molecular framework for study on the pathophysiology of systemic inflammation induced by injuries.;The overall studies were divided into single injury in which the animals were subjected to single burn injury or single cecal ligation and puncture (CLP) injury individually and "double hits" injury in which the rats were subjected to a burn injury and subsequent CLP injury. Animals were sacrificed at various time points, and whole liver samples were analyzed using Affymetrix Rat Genome 230 2.0 Arrays. After identifying differentially expressed probesets in injury rats vs. sham over time, the concatenated data sets corresponding to these differentially expressed probesets in injury and sham were combined and analyzed using a "consensus clustering" approaches. Ingenuity Pathway Analysis (IPA) was used to functionally annotate genes, and RT-PCR was used to confirm microarray trends.;Both single burn and CLP injury induces the activation of pro-inflammatory response, anti-inflammatory response, and enhanced synthesis of acute-phase proteins, increased metabolism and tissue damage. Genes which are directly in response to bacteria removal are only triggered in CLP injury. In double hits study, burn priming prior to CLP disrupts the transcriptional response in the liver to septic injury in the rat by altering the onset of anti-bacterial functions in the liver. In addition, burn enhanced hyper metabolic conditions through aggressive amino acid degradation at critical time points. |
