Erythromycin has therapeutic efficacy on muscle fatigue acting specifically on orosomucoid to increase muscle bioenergetics and physiological parameters of endurance
Erythromycin has therapeutic efficacy on muscle fatigue acting specifically on orosomucoid to increase muscle bioenergetics and physiological parameters of endurance
复制标题
红霉素对肌肉疲劳具有治疗功效，特别作用于口红霉素，可增加肌肉生物能和耐力的生理参数
DOI：
10.1016/j.phrs.2020.105118
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发表时间：
2020
影响因子：
9.3
通讯作者：
Xia Liu
中科院分区：
文献类型：
--
作者：
Jingjing Wan;Zhen Qin;Hong Lei;Pengyuan Wang;Yu Zhang;Jiayi Feng;Jie Wei;Yang Sun;Xia Liu
目前，对于肌肉疲劳的治疗，还没有官方或半官方的建议。我们曾报道过急性时相蛋白类粘蛋白（ORM）具有增强肌肉耐力和抗疲劳的作用。在试图寻找针对ORM的抗疲劳药物时，我们发现大环内酯类抗生素，特别是红霉素，是有效的。红霉素能显著延长小鼠强迫游泳和跑台运动的时间，增加肌肉疲劳指数，减轻疲劳引起的组织损伤，提高肌肉糖原含量、线粒体功能和ATP水平。红霉素在体外和体内均以剂量和时间依赖的方式增加ORM蛋白的表达.进一步的研究发现，红霉素能提高ORM启动子的活性和ORM mRNA的稳定性，这可能是ORM上调的原因。ORM基因敲除或敲除可消除红霉素对小鼠强迫游泳时间、肌疲劳指数和糖原水平的促进作用。此外，在给予C-C基序趋化因子受体5（CCR 5）拮抗剂或AMPKα2缺乏的小鼠中，这些作用也被消除。因此，红霉素可通过上调ORM水平，激活CCR 5-AMPK通路，提高肌糖原含量，增强肌耐力，有望成为一种治疗肌肉疲劳的药物。
At present, there are still no official or semi-official recommendations for the treatment of muscle fatigue. We previously reported that acute phase protein orosomucoid (ORM) can enhance muscle endurance and exert anti-fatigue effect. In attempting to seek anti-fatigue drugs that target ORM, we found macrolide antibiotics, particularly erythromycin, were effective. Erythromycin can significantly prolong the time of mice forced-swimming and treadmill running, increase muscle fatigue index, alleviate fatigue-induced tissue damage, and elevate glycogen content, mitochondria function and ATP level in the muscle. Also, erythromycin increases ORM protein expression in a dose- and time- dependent manner bothin vitroandin vivo. Further studies found that erythromycin could increase the activity of ORM promoter and the stability of ORM mRNA, which might both be responsible for the ORM up-regulation. ORM knockdown or knockout could abolish the promoting effect of erythromycin in mice forced-swimming time, muscle fatigue index and glycogen level. Furthermore, those effects were also abolished in mice with C-C motif chemokine receptor 5 (CCR5) antagonist administration or AMPKα2 deficiency. Therefore, erythromycin could enhance muscle glycogen and endurance via up-regulating the level of ORM and activating CCR5-AMPK pathway, indicating it might act as a potential drug to treat muscle fatigue.