Objective: To study the effect of insulin intensive treatment on hyper-proteolysis of skeletal muscle in scalded rabbit with sepsis.
Methods: Male white rabbits were randomly divided into scald group (S group), scald sepsis group (SS group), scald with insulin treatment group (SI group), scald sepsis with insulin treatment group (SSI group), and control group (C group), with 6 animals in each group. The extent of scald injury was 30% total body surface area (TBSA) III degree in depth, and the model of scald sepsis was replicated by administration of endotoxin (2 mg/kg) into the peritoneal cavity immediately after scald injury. Insulin intensive treatment was given with injection of insulin to keep the plasma glucose level in physiologic range (4.4-6.1 mmol/L) for SI group and SSI group. The contents of 3-methylhistidine (3-MH) in extensor digitorum longus (EDL) muscles and urine were determined with high performance liquid chromatography. The expressions of ubiquitin mRNA in the EDL muscle were assessed with Northern blot analysis.
Results: The contents of 3-MH in EDL muscles and urine of S group and SS group were increased significantly as compared with C group (all P<0.01), and that of SI group and SSI group were decreased markedly compared with S group and SS group (all P<0.01), respectively. The mRNA expression of ubiquitin of S group and SS group was enhanced significantly compared with C group (all P<0.01), and that of SI group and SSI group was down-regulated notably compared with S group and SS group (all P<0.01), respectively.
Conclusion: The activity of ubiquitin system, one of important protein degradation pathways, and the proteolysis in skeletal muscle are enhanced after scald injury, especially so sepsis sets in, and insulin intensive treatment can effectively alleviate hyper-proteolysis of skeletal muscle through inhibiting the activity of ubiquitin system at gene level.