Pre-moderate-intensity Aerobic Exercise Reduces the Level of TNF-R1 in Skeletal Muscle of Mice and Protects Against Doxorubicin-induced Skeletal Muscle Atrophy
Objective The purpose of this study was to explore whether long-term moderate intensity aerobic exercise before doxorubicin(DOX)administration can reduce TNF-α and its receptor TNF-R1 levels in skeletal muscle to resist DOX-induced skeletal muscle atrophy,to provide a certain theoretical basis for exercise to avoid chemotherapy side effects.Methods Thirty-six 3-month-old male C57BL/6 mice were randomly separated into sedentary group(SED)and exercise group(EXE)after they adapted to the environment.The EXE mice were given moderate intensity treadmill running for 8 weeks,and the SED mice were fed normally.After the last exercise,6 mice randomly selected from both SED group and EXE group and then sacrificed.The remaining mice,SED group were grouped into normal saline group(SED-SAL)and DOX chemotherapy group(SED-DOX),and EXE mice were grouped into normal saline group after exercise(EXE-SAL)and DOX chemotherapy group after exercise(EXE-DOX).The SED-DOX group and EXE-DOX group were treated with DOX chemotherapy intraperitoneally for two weeks.And the SED-SAL group and EXE-SAL group were injected with normal saline of corresponding volume.At the end of chemotherapy,all four groups sacrificed.Bilateral quadriceps femoris muscle were removed and used H&E staining to calculate the cross-sectional area(CSA)of muscle fibers,used ELISA to detect TNF-αlevels of plasma,and used WB to detect the protein expression levels of TNF-α,TNF-R1,PGC-1α,MuRF-1,Caspase-8.Results(1)Compared with the mice injected with normal saline,the body weight,quadriceps femoris muscle mass,maximum running speed,the number of type Ⅰ muscle fiber and muscle fiber CSA of the mice injected with DOX were significantly decreased,indicating that DOX administration caused skeletal muscle atrophy.However,8-week moderate-intensity aerobic exercise intervention before DOX administration can reduce a series of skeletal muscle adverse reactions caused by DOX.(2)Compared with the mice injected with normal saline,the level of TNF-α in plasma,the levels of TNF-αand TNF-R1 in quadriceps femoris of the mice injected with DOX were significantly increased,and the protein expression levels of MuRF-1 and Caspase-8 in quadriceps femoris were also significantly increased.While 8-week moderate intensity aerobic exercise before chemotherapy can significantly inhibit the expression of TNF-α,TNF-R1,MuRF-1 and Caspase-8 in quadriceps.(3)8-week moderate-intensity aerobic exercise increased the maximum running speed,activated PGC-1α,improved the activity of mitochondria-related proteins,and inhibited the expression of TNF-α and TNF-R1 in quadriceps femoris of mice.Conclusion 8-week moderate intensity aerobic exercise intervention before DOX administration can inhibit TNF-α and TNF-R1 expression level in quadriceps femoris and inhibit the protein degradation and apoptosis reaction which may be the downstream of TNF-α/TNF-R1 pathway.This might be one of the potential pathways for exercise to resistance to doxorubicin-induced quadriceps femoris atrophy in mice.
维普
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