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Updated: Aug 14, 2026
A Preclinical Model of Sepsis-Induced Myopathy with Disuse in Mice
Published on: June 14, 2024
[Clinical study of skeletal muscle proteolysis in severely burned patients with sepsis]
Jia-ke Chai1, Chuan-an Shen, Zhi-yong Sheng
1Burns Institute, Department of Burn and Plastic Surgery, First Hospital Affiliated to General Hospital of Chinese People's Liberation Army, Beijing 100037, China.
Objective:
To study the changes of skeletal muscle proteolysis in severely burned patients with sepsis and analyze its possible mechanism.
Methods:
Blood samples were collected from 20 burned patients with sepsis, aged 42 +/- 10 (burn sepsis group), and 12 patients undergoing plastic operation after burn, aged 43 +/- 8 (control group) to determine the plasma concentrations of cortisol and tumor necrosis factor (TNF-alpha) by radioimmunoassay. 24 h urine was retained to determine the level of 3-methylhistidine (3-MH) by high performance liquid chromatography. An appropriate amount of quadriceps femoris muscle sample was collected during operation to determine the concentration of 3-methylhistidine with high performance liquid chromatography, the expression of ubiquitin mRNA, E(2)-14k mRNA and C(2) subunit mRNA by Northern blot analysis, and the protein expression of C(2) subunit by Western blot analysis.
Results:
The plasma concentrations of cortisol and TNF-alpha in the burn sepsis group were 478 +/- 56 microg/L and 22.4 +/- 3.8 microg/L respectively, both significantly higher than the those in the normal control group, 72 +/- 12 microg/L and 0.5 +/- 0.1 microg/L respectively (both P < 0.01). The amount of 3-MH in the quadriceps femoris muscle of the burn sepsis group was 4.3 +/- 0.6 micromol/g, significantly higher than that of the control group (2.5 +/- 0.4 micromol/g, P < 0.01). The 24 h urinary output of 3-MH of the burn sepsis group was 456 +/- 25 micromol, significantly higher than that of the control group (202 +/- 29 micromol, P < 0.091). The expressions of ubiquitin mRNA 2.4 Kilobase pair (kb) and 1.2 kb, E(2)-14k mRNA 1.2 kb and C(2) subunit mRNA in quadriceps femoris muscles of the burn sepsis group were increased with 51%, 32%, 75%, and 39% respectively, as compared with those of the control group (all P < 0.01). The protein expression of C(2) subunit in quadriceps femoris muscles of the burn sepsis group was increased with 130% than that of the control group (P < 0.01).
Conclusion:
The proteolytic rate in skeletal muscle is increased during sepsis after severe burn and the mechanism is related to the enhanced function of the ubiquitin system at both gene and protein levels with the hypersecretion of glucocorticoid and TNF-alpha.
