Trimetazidine Attenuates Dexamethasone-Induced Muscle Atrophy via Inhibiting NLRP3/GSDMD Pathway-Mediated Pyroptosis

• DOI: 10.20944/preprints202012.0643.v1
• Publication Date: 2020-12-28T03:04:50Z
• Authors: Li Wang; Ming-Qing He; Xi-Yu Shen; Kang-Zhen Zhang; Can Zhao; Li Liu; Man Wang; Yun-Ling Bu; Jia-Wen Li; Fan Xu; Hui-Wei He; Xiang Lu; Wei Gao
• Keywords: Pyroptosis; Trimetazidine; Muscle Atrophy; C2C12

Skeletal muscle atrophy is one of the major side effects high dose or sustained usage glucocorticoids. Pyroptosis a novel form pro-inflammatory programmed cell death that may contribute to skeletal injury. Trimetazidine, well-known anti-anginal agent, can also improve performance both in human and mice. We here showed dexamethasone induced atrophy, evidenced by increase F-box (Atrogin-1) ring finger 1 (MuRF1) expression , decrease myotube diameter C2C12 myotubes. Dexamethasone pyroptosis, indicated upregulated pyroptosis-related protein NLRP3, Caspase-1 GSDMD. Knockdown NLRP3 GSDMD attenuated dexamethasone-induced pyroptosis atrophy. Trimetazidine administration ameliorated vivo vitro. Moreover, trimetazidine improved exercise tolerance, as increased running distance time, well mass dexamethasone-treated Mechanically, could reverse activation myotubes Taken together, our present study demonstrated NLRP3/GSDMD pathway-mediated was involved partially alleviate via inhibiting pyroptosis. Thus, might be potential therapeutic compound for prevention glucocorticoid-treated patients.