| Wound sepsis remains to be the leading cause of death in critically burned patients. Studies have shown that almost all the septic patients have hypermetabolism which contributes to the development of multiple organs dysfunction syndrome (MODS). However, most of previous studies concerning hypermetabolism concentrate on protein, very little attention was put on lipid. Recent studies reveal that lipid metabolic disturbance is involved in hypermetabolism, in which liver plays a pivotal role. The present experiment study was designed to investigate the effect of burn wound sepsis on lipid metabolism and explore the molecular mechanism of perturbation in lipid metabolism during sepsis stage. Materials and methods100 male Wistar rats were fed a standard diet for one week before the studies began. The animals were scalded resulting in 30% TBSA full-thickness bum and then randomly divided into wound sepsis group and scald group (control group). Pseudomonas aeruginosa (109/ml) was inoculated to the rats' wounds of sepsis group. Through observing the life conditions, the appearance of wound, the quantity of bacteria in the subeschar tissue and pathological changes, we confirmed that the rat model of bum wound sepsis was established successfully. Blood samples and fresh liver tissues were obtained, fresh liver tissues were rapidly dissected frozen in liquid nitrogen and stored at -70 °C. The contents of adenosine triphosphate (ATP), triglyceride (TG) and malondialdehyde (MDA) in liver, and the levels of LPS, free fatty acid (FFA), TG and ALT in plasma were sequentially determined and analyzed at different time point. Total RNA of liver was isolated with Trizol. We used cDNA and oligonucleotide-arrays to compare the expression of different genes in liver of rats. Radio-labeled cDNA from liver of control and wound sepsis rats werehybridized to arrays. According to the results of DNA arrays, the levels of liver PPARa and target genes mRNA were measured by reverse transcription polymerase chain reaction (RT-PCR). ResultsThe contents of ATP in the liver decreased rapidly postburn. The contents of ATP in sepsis group were lower than control group obviously. Significant negative correlations between the contents ATP in liver and levels of LPS in plasma were noted. Severe function damage and lipid accumulation in liver were observed in sepsis group.By comparing expression profile of the two groups, the mRNA levels of 9 genes which related to lipid metabolism were found to be altered by sepsis. Among fatty acid transport, fatty acid oxidation, lipid synthesis and metabolism, transcriptional regulation, lipoprotein metabolism and cholesterol metabolism were identified.Liver PPARa and L-CPT1 gene expression were decreased and were lower than control group obviously, meanwhile the accumulation of TG and a reduction of ATP in liver were manifested in the development of burn wound sepsis. Discussion and conclusionsAccording to above results, conclusion can be made that burn wound sepsis increased energy expenditure, and promoted lipid metabolism disturbance. Several processes of lipid metabolism in liver were changed by the effect of sepsis.PPARa is expressed primarily in tissues that have a high level of fatty acid catabolism, such as liver, brown fat, kidney, heart, and skeletal muscle, also participates in fatty acid oxidation. This experiment observed the relationship between the PPARa and L-CPT1 mRNA expression in liver of rat.PPARa is ligand-depended transcription factor and is expressed most in liver. The accumulation of lipid can induce the expression of PPARa target gene. These genes are a relativity homogenous group of genes that participate in aspects of lipid catabolism such as fatty acid uptake through membranes, fatty acid binding in cells, fatty acid oxidation and lipoprotein assembly and transport. These results...
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