Effect of Astaxanthin on Exercise-induced Skeletal Muscle Damage in Rats through AMPK/mTOR/ULK1 Autophagy Pathway
Objective:To explore the effects of astaxanthin on EIMD in rats based on the AMPK/mTOR/ULK1 pathway.Methods:Healthy male SD rats were randomly divided into a control(C)group,exercise(E)group,astaxanthin(M)group,exercise+astaxanthin(EM)group,exercise+AICAR(EA)group,exercise+astaxanthin+AICAR(EMA)group,and exercise+astaxanthin+MHY1485(EMM)group,with 10 rats in each group.Groups M,EM,EMA,and EMM were given astaxanthin;Groups C and E were given soybean oil;Groups EA and EMA were injected with AICAR;Group EMM was injected with MHY1485;Groups E,EM,EA,EMA,and EMM proceeded with exhaustive exercise,and the other groups were fed quietly.HE staining was used to observe the pathological changes in soleus tissues.The contents of MDA,SOD,IL-6,IL-1β,CK,and FINS in serum were detected by ELISA.mRNA expression of related indexes in soleus was detected by RT-PCR.Phosphorylation levels of the AMPK/mTOR/ULK1 autophagy pathway and apoptin expression in soleus were detected by Western blot.FBG and LA levels were detected,and ISI and HOMA-IR were calculated.The role of LA,MDA,IL-6,and IL-1β in EIMD and ISI was investigated by mediating effect analysis.Results:Compared with group C,the contents of MDA,IL-6,IL-1β,CK,LA,FBG,FINS,and HOMA-IR in the serum of group E were significantly increased,while SOD and ISI were significantly decreased;The expression levels of p-AMPK Thr172,p-mTOR Ser2448,p-ULK1 Ser555,p-ULK1 Ser757,and P62 were significantly increased,while the expression levels of LC3-Ⅱ,ILC3-Ⅱ/LC3-I and BCL2/BAX were significantly decreased.After gavage of astaxanthin or injection of AICAR,the above changes could be reversed.The reverse effect was more obvious in the EMA group than in the groups EA and EM.However,the dual intervention of astaxanthin and MHY1485 to exhaustive exercise rats blocked the protective effect of astaxanthin on EIMD.In addition,MDA,IL-6,and IL-1β played a partial mediating effect on EIMD and ISI caused by LA.Conclusion:Exhaustive exercise can cause EIMD,and the pathogenesis involves lactic acid accumulation,oxidative stress,inflammation,and apoptosis.At this time,insulin resistance increases,and the ability of skeletal muscle to take up and utilize glucose decreases,which will up-regulate mTOR activity,inhibit autophagy flux,and aggravate muscle injury.Astaxanthin can regulate the mTOR-ULK1 autophagy pathway to alleviate EIMD,and the combined effect of astaxanthin and AICAR is more beneficial to EIMD.
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