Salidroside Attenuates Denervation-Induced Skeletal Muscle Atrophy Through Negative Regulation of Pro-inflammatory Cytokine

Salidroside Attenuates Denervation-Induced Skeletal Muscle Atrophy Through Negative Regulation of Pro-inflammatory Cytokine
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红景天苷通过促炎细胞因子的负调节减轻去神经引起的骨骼肌萎缩

DOI:
10.3389/fphys.2019.00665
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发表时间:
2019
影响因子:
4
通讯作者:
Sun Hualin
Sun Hualin
中科院分区:
医学2区
文献类型:
--
作者:
Wu Changyue;Tang Longhai;Ni Xuejun;Xu Tongtong;Fang Qingqing;Xu Lai;Ma Wenjing;Yang Xiaoming;Sun Hualin

文献摘要

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骨骼肌萎缩与促炎细胞因子有关。红景天苷是红景天的一种生物活性成分,具有抗炎作用。然而,关于红景天苷对失神经诱导的肌肉萎缩的影响知之甚少。因此,本研究旨在确定红景天苷是否可以防止失神经诱导的肌肉萎缩,并阐明潜在的分子机制。失神经支配导致骨骼肌内炎性因子进行性积聚,尤其是白细胞介素6(IL 6)及其受体,局部注射重组小鼠IL 6(rmIL 6)可诱导靶肌肉萎缩,提示失神经支配可诱导靶肌肉炎症反应,炎症反应可引发肌肉萎缩。红景天苷可减轻失神经诱导的肌肉萎缩,抑制IL 6的产生。此外,在用红景天苷处理的失神经肌肉中观察到信号转导和转录激活因子3(STAT 3)的磷酸化的抑制,以及细胞因子信号传导抑制因子(SOCS 3)、肌肉环指蛋白-1(MuRF 1)、萎缩F盒(atrogin-1)、微管相关蛋白轻链3 β(LC 3B)和PTEN诱导的推定激酶(PINK 1)的水平降低。最后,所有这些反应红景天苷复制中和抗体对IL 6。综上所述,这些结果表明红景天苷减轻了去神经诱导的炎症反应,从而抑制肌肉蛋白水解和肌肉萎缩。因此,推测红景天苷可能是预防肌肉萎缩的潜在治疗候选物。
Skeletal muscle atrophy is associated with pro-inflammatory cytokines. Salidroside is a biologically active ingredient of Rhodiola rosea, which exhibits anti-inflammatory property. However, there is little known about the effect of salidroside on denervation-induced muscle atrophy. Therefore, the present study aimed to determine whether salidroside could protect against denervation-induced muscle atrophy and to clarify potential molecular mechanisms. Denervation caused progressive accumulation of inflammatory factors in skeletal muscle, especially interleukin 6 (IL6) and its receptor, and recombinant murine IL6 (rmIL6) local infusion could induce target muscle atrophy, suggesting that denervation induced inflammation in target muscles and the inflammation may trigger muscle wasting. Salidroside alleviated denervation-induced muscle atrophy and inhibited the production of IL6. Furthermore, the inhibition of phosphorylation of signal transducer and activator of transcription 3 (STAT3), and the decreased levels of suppressor of cytokine signaling (SOCS3), muscle RING finger protein-1 (MuRF1), atrophy F-box (atrogin-1), microtubule-associated protein light chain 3 beta (LC3B) and PTEN-induced putative kinase (PINK1) were observed in denervated muscles that were treated with salidroside. Finally, all of these responses to salidroside were replicated in neutralizing antibody against IL6. Taken together, these results suggest that salidroside alleviates denervation-induced inflammation response, thereby inhibits muscle proteolysis and muscle atrophy. Therefore, it was assumed that salidroside might be a potential therapeutic candidate to prevent muscle wasting.