Abstract:
Objective: To determinethe changes in proteolytic rate and mRNA expression of ubiquitin in rat skeletal muscle, and investigate the molecular mechanism of skeletal muscle protein catabolism during sepsis.
Methods: The ratswith sepsis was established by administering endotoxin into theperitonealcavity. The rats were randomly divided into 4 groups as follows: 2h, 6h, 12hand 24h after administration of endotoxin, 16 animals for each group including 8 normal controls. We use the in vitro muscle incubation system with sufficient oxygen supply as well as amino acid automatic analyzer for detection of the proteolytic rate of extensor digitorium longus(EDL) muscle in the samples. The mRNA expression of ubiquitin in rat EDL muscle was determined by northern blot analysis.
Results: Total proteolytic rate in EDL muscle increased slightly at 2h and 6h after administering endotoxin into theperitonealcavity, no statistically significant difference was observed at 12h and 24h,there was a progressive 1~2-fold increase in myofibrillar proteolytic rate at 2h and 6h, 40% increase at 12h, respectively, as compared with that of normal control(
P<0.01). Ubiquitin mRNA-2.4kb rose by 2~5-fold at 2h and 6h after administering endotoxin into theperitonealcavity(
P<0.01), but not at 12h and 24hcompared with that of normal control. There was no statistically significant changein ubiquitin mRNA-1.2kb.Significantly positive correlation between myofibrillar proteolysis and expression of ubiquitin mRNA-2.4kb was observed(
r=0.9731,
P=0.003).
Conclusion: The enhancement in skeletal muscle proteolysis is probably relative to activation of ubiquitin-proteasome pathway.