Myostatin antisense administration prevents sepsis-induced muscle atrophy and weakness in male mice.

Muscle atrophy and weakness are serious problems associated with sepsis. However, only a few pharmacological interventions are available to date. In this study, myostatin antisense was used to prevent sepsis-induced muscle atrophy and weakness. Sepsis was induced in 8-week-old male C57BL/6J mice via intraperitoneal injection of 1 mg/g cecal slurry (CS). Myostatin antisense was injected into the right tibialis anterior muscle. Myostatin mRNA was measured in the tibialis anterior and quadriceps femoris muscles on Day 1. The body weight, grip strength, and cross-sectional area of the tibialis anterior muscle were measured on Day 6. The administration of myostatin antisense decreased myostatin expression on Day 1 in the injected side (0.023 ± 0.010 in CS vs. 0.008 ± 0.002 in CS + antisense) as well as in the noninjected muscles. It also decreased the myostatin protein level (2.0 ± 0.3 in CS vs. 1.2 ± 0.5 in CS + antisense, p = 0.04). Body weight reduction (94.9% ± 2.0% vs. 98.2% ± 1.8%, p < 0.01) and grip strength reduction (77.0% ± 12.3%vs. 89.8% ± 8.3%, p = 0.04) were suppressed by the injection. The cross-sectional area of the right tibialis anterior muscle increased after the treatment (1116 ± 530 μm2 vs. 1435 ± 648 μm2, p < 0.01). Myostatin antisense suppressed the elevation of myostatin mRNA expression in whole muscles of mice with sepsis and prevented sepsis-induced muscle atrophy and weakness.