Zhonghua Shao Shang Za Zhi. 2021 Mar 3;37(3):1-8. doi: 10.3760/cma.j.cn501120-20200120-00030. Online ahead of print.
ABSTRACT
Objective: To observe the functional changes of skeletal muscle in severely burned rats, and investigate the possible effects and mechanisms of Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway inhibitors on skeletal muscle function. Methods: The experiment research method was applied. One hundred and twenty male Wistar rats of 8-weeks-old were divided into sham injury group, simple burn group, and burn+JAK/STAT3 inhibitor group according to the random number table, with 40 rats in each group. Rats in simple burn group and burn+JAK/STAT3 inhibitor group were inflicted with 50% total body surface area full-thickness scald in back and abdomen, and rats in sham injury group were sham injured. Rats in burn+JAK/STAT3 inhibitor group were intraperitoneally injected with JAK/STAT3 inhibitor ruxolitinib. On post injury day (PID) 0, 1, 4, 7, and 14, 8 rats in each group were used to measure the specific force generated by extensor digitorum longus in optimal length stimulated with pulse frequency of 20, 40, 60, 80, 100, 120, 140, 160 Hz using a multichannel electrophysiological instrument, and specific force in fatigue period of extensor digitorum longus in optimal length stimulated with pulse frequency of 50 Hz for 0, 10, 20, 30, 60, 120, 180, 240, 300 s. On PID 0, 1, 4, 7, and 14, carbonyl compound content of extensor digitorum longus was determined by ultraviolet spectrophotometry, and ATP content of extensor digitorum longus was determined by micrometry. Data were statistically analyzed with analysis of variance for factorial design, Bonferroni test, and t test. Results: (1) Compared with sham injury group, specific forces of extensor digitorum longus of rats in simple burn group were significantly decreased after stimulated with all the pulse frequency on PID 0, 1, 7, and all the pulse frequency except for 20 Hz on PID 4, and pulse frequency of 20 and 40 Hz on PID 14 (P<0.05 or P<0.01). Compared with simple burn group, specific forces of extensor digitorum longus of rats in burn+JAK/STAT3 inhibitor group were significantly increased after stimulated with all pulse frequency except for 20 Hz on PID 1 and all the pulse frequency on PID 4, 7, and 14 (P<0.05 or P<0.01). (2) Compared with sham injury group, specific forces of extensor digitorum longus of rats in simple burn group were significantly decreased in fatigue period at all the stimulation time points except for 240 s on PID 7 (P<0.05 or P<0.01). Compared with simple burn group, specific forces of extensor digitorum longus of rats in burn+JAK/STAT3 inhibitor group were significantly increased in fatigue period at all stimulation time points except for 240 s on PID 4, and all stimulation time points on PID 7 and 14 (P<0.05 or P<0.01). (3) The carbonyl compound content of extensor digitorum longus of rats in simple burn group on PID 0, 1, 4, 7, and 14 was (0.651±0.155), (0.739±0.194), (0.618±0.086), (0.813±0.162), (0.615±0.115) nmol/mg, which were significantly higher than (0.196±0.0190, (0.156±0.004), (0.169±0.023) (0.156±0.027), (0.175±0.008) nmol/mg of rats in simple burn group (t=7.219, 6.491, 10.938, 9.182, 11.589, P<0.01) and (0.538±0.069), (0.369±0.059), (0.273±0.061), (0.334±0.109), (0.318±0.101) nmol/mg of rats in burn+JAK/STAT3 inhibitor group (t=2.446, 4.689, 8.355, 5.754, 6.097, P<0.05 or P<0.01). (4) The ATP content in extensor digitorum longus of rats in simple burn group on PID 1, 4, 7, and 14 was significantly lower than that in sham injury group (t=7.159, 7.591, 7.473, 4.026, P<0.01) and burn+JAK/STAT3 inhibitor group (t=2.295, 2.575, 2.453, 2.997, P<0.05). Conclusions: After severe burn, the specific force of extensor digitorum longus in rat decreased significantly after stimulated with different pulse frequencies, and the extensor digitorum longus in rat was prone to fatigue. Blocking the JAK/STAT3 signaling pathway could reduce the oxidative stress of muscle protein and increase ATP content, thereby reducing the muscle strength decline caused by burn and improving the muscle strength decline during fatigue.
PMID:33706427 | DOI:10.3760/cma.j.cn501120-20200120-00030
