[Study on the mechanism of the effects of recombinant rat tumor necrosis factor alpha on the degradation of rat skeletal muscle proteins].

Objective: To investigate the mechanism and the effects of intravenously injected tumor necrosis factor alpha (TNFalpha) on skeletal muscle protein degradation in rats and its relationship with glucocorticoid.

Methods: Forty-five male Wistar rats were randomly divided into 3 groups as A (control), B (TNFalpha injection) and C (TNFalpha and glucocorticoid receptor antagonist injection) groups. TNFalpha in dose of 1x 10(6) units/kg was given to rats in B group intravenously. RU38486, a glucocorticoid receptor antagonist, was given by gavage in C group 2 hours before intravenous injection of TNFalpha in the same dose as in B group. the rat temperature was monitored 12 hours after the administration of the drugs. At the same time, the rat extensor digitorum longus muscles (EDL) were isolated, weighed and cultured under aerobic condition, and than the degradation rates of total and the myofibrillar proteins were determined with HPLC (high performance liquid chromatography), and the expression changes in C2 subunit mRNA and ubiquitin mRNA were detected by Northern blot.

Results: Twelve hours after the injection, the temperature of the rats in B and C group was much higher than that in A group (P < 0.01), while the weight of the extensor digitorum longus muscle in B and C groups was evidently lower than that in A group (P < 0.01) whereas that in C was higher than that in B groups (P < 0.05). The degradation rates of total and the myofibrillar proteins in B group were increased by 43% and 112%, respectively, when compared with those in A group (P < 0.01), while the rates in C group was decreased by 16% and 28%, respectively, when compared with those in B group (P < 0.01). In addition, the expressions of ubiquitin mRNA (2.4 kb) and C2 subunit mRNA in B group were increased 4.3 and 3.6 fold compared with those in A group, whereas those in C group were much lower than those in B group.

Conclusion: Intravenous injection of recombinant TNFalpha in large dose might enhance the activity of rat skeletal muscle ubiquitin-proteasome system pathway, which led to an increase in the degradation rate of rat total protein, especially the myofibrillar protein. Glucocorticoid was one of the mediating factors of that effect.