Effect of electroacupuncture on denervated skeletal muscle atrophy in rats based on p38 MAPK signaling pathway
Objective To assess the impacts of electroacupuncture (EA) on the gait,oxidative stress,inflammatory reaction,and protein degradation in the rats of denervated skeletal muscle atrophy,and explore the potential mechanism of EA for alleviating denervated skeletal muscle atrophy.Methods Forty male SD rats,8 weeks old,were randomly assigned to a sham-surgery group,a model group,an EA group,and a p38 MAPK inhibitor group,with 10 rats in each group.The right sciatic nerve was transected to establish a rat model of denervated skeletal muscle atrophy in the model group,the EA group and the p38 MAPK inhibitor group.In the sham-surgery group,the nerve was exposed without transection.One day after successful modeling,the rats in the EA group received EA at "Huantiao" (GB30) and "Zusanli" (ST36) on the right side,using a continuous wave with a frequency of 2 Hz and current intensity of 1 mA,for 15 min in each session,EA was delivered once a day,6 times a week.In the p38 MAPK inhibitor group,the rats received the intraperitoneal injection with SB203580 (5 mg/kg),once a day,6 times a week.The intervention was composed of 3 weeks in each group.After the intervention completion,the CatWalk XT 10.6 animal gait analysis system was used to record the gait parameters of rats.The wet weight ratio of the gastrocnemius muscle was calculated after the sample collected.Using HE staining,the fiber morphology and cross-sectional area of the gastrocnemius muscle were observed;ELISA was employed to measure the content of interleukin (IL)-6,IL-1β,and tumor necrosis factor (TNF)-α in the gastrocnemius muscle;the biochemical hydroxyamine method was adopted to detect the content of superoxide dismutase (SOD) and malondialdehyde (MDA) in the gastrocnemius muscle;with immunohistochemistry and Western blot used,the expression of p38 mitogen-activated protein kinase (p38 MAPK),phosphorylated (p)-p38 MAPK,muscle atrophy F-box gene (Atrogin-1),muscle RING finger 1 (Murf-1),nuclear factor E2-related factor 2 (Nrf2),and heme oxygenase-1 (HO-1) was detected in the gastrocnemius muscle.Results Compared to the sham-surgery group,in the model group,the standing duration,the swing time and the step cycle were increased (P<0.001),the footprint area of the maximum contact time,the print area,the average intensity of the maximum contact time,the average intensity,the swing speed,and the step length were decreased (P<0.001);the wet weight ratio of gastrocnemius muscle and fiber cross-sectional area were reduced (P<0.001);the content of IL-6,IL-1β,TNF-α and MDA in gastrocnemius muscle elevated (P<0.001),and that of SOD reduced (P<0.001);the positive and protein expression of p-p38 MAPK,Atrogin-1 and Murf-1 elevated (P<0.001) and that of Nrf2 and HO-1 dropped (P<0.001).When compared with the model group,in the EA group and the p38 MAPK inhibitor group,the standing duration,the swing time and the step cycle decreased (P<0.01),the footprint area of the maximum contact time,the print area,the average intensity of the maximum contact time,the average intensity,the swing speed,and the step length increased (P<0.01);the wet weight ratio of gastrocnemius muscle and fiber cross-sectional area were improved (P<0.01,P<0.05);the content of IL-6,IL-1β,TNF-α and MDA in gastrocnemius muscle dropped (P<0.05,P<0.01),and that of SOD elevated (P<0.01,P<0.05);the positive and protein expression of p-p38 MAPK,Atrogin-1 and Murf-1 dropped (P<0.01,P<0.05) and that of Nrf2 and HO-1 increased (P<0.01,P<0.05).Conclusion Electroacupuncture may alleviate skeletal muscle atrophy in denervated skeletal muscle atrophy rats by mediating the p38 MAPK activity,thereby suppressing oxidative stress,inflammatory reaction,and protein degradation.
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