Department of Chinese Materia Medica, School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing 100019, P.R. China.
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Institute of Radiation Medicine, Beijing 102206, P.R. China.
Mol Med Rep. 2017 Oct;16(4):5165-5174. doi: 10.3892/mmr.2017.7287. Epub 2017 Aug 18.
Microgravity has been previously demonstrated to induce skeletal muscle atrophy, loss of muscle force and disorders in myogenesis and metabolism. Current pharmacological strategies exhibit poor efficacy. Bu Zhong Yi Qi decoction (BZ) is a well‑known traditional Chinese medicine decoction used for myasthenia gravis. In the present study, its effect on unloading induced muscle atrophy was investigated. The mousetail suspension model was used to simulate weightlessness induced muscle atrophy. The results indicated that BZ could significantly protect muscles from simulated weightlessness‑induced atrophy. To elucidate the underlying mechanisms, drugCIPHER‑CS methods were introduced to predict its potential targets, significantly enriched pathways and biological processes. The results demonstrated that the calcium signaling pathway, citrate cycle, biosynthetic and lipid metabolic process are affected by BZ. Among the targets, nuclear receptor corepressor 1 (NCoR1) is one of the most important proteins involved in myogenesis and metabolism. The results indicated that BZ significantly downregulated NCoR 1 expression, and further induced muscle differentiation and metabolism by regulating NCoR1‑associated gene expression in vivo and in vitro. In summary, the present study indicated that may be effective in combating weightlessness‑induced muscle atrophy. Combined with bioinformatics, the underlying mechanism for this decoction was investigated, which provided an improved understanding of this decoction.
先前的研究已经证实,微重力会导致骨骼肌萎缩、肌力丧失以及肌肉生成和代谢紊乱。目前的药理学策略显示出较差的疗效。补中益气汤(BZ)是一种著名的中药方剂,用于治疗重症肌无力。在本研究中,研究了其对抗失重大鼠骨骼肌萎缩的作用。利用鼠尾悬吊模型模拟失重引起的肌肉萎缩。结果表明,BZ 可显著保护肌肉免受模拟失重引起的萎缩。为了阐明潜在的机制,引入了 drugCIPHER-CS 方法来预测其潜在的靶点、显著富集的途径和生物学过程。结果表明,BZ 影响钙信号通路、柠檬酸循环、生物合成和脂质代谢过程。在这些靶点中,核受体共抑制因子 1(NCoR1)是参与肌肉生成和代谢的最重要的蛋白质之一。结果表明,BZ 显著下调 NCoR1 的表达,并通过调节 NCoR1 相关基因的表达,在体内和体外进一步诱导肌肉分化和代谢。综上所述,该研究表明 BZ 可能对对抗失重大鼠骨骼肌萎缩有效。结合生物信息学,研究了该方剂的潜在作用机制,从而加深了对该方剂的理解。