南方医科大学学报2025，Vol.45Issue(3)：603-613,11.DOI:10.12122/j.issn.1673-4254.2025.03.18
右美托咪定通过激活Nrf2/HO-1通路减轻热应激诱导的人骨骼肌细胞胀亡
Dexmedetomidine attenuates heat stress-induced oncosis in human skeletal muscle cells by activating the Nrf2/Ho-1 pathway
摘要
Abstract
Objective To investigate the protective effects of dexmedetomidine(DEX)against heat stress(HS)-induced oncosis in human skeletal muscle cells(HSKMCs)and its underlying mechanisms.Methods A HSKMC model of HS-induced oncosis were established by 43℃water bath for 4 h,and the effects of treatments with 30 μmol/L DEX,ML385(a Nrf2 inhibitor)+DEX,si-Nrf2+HS,and si-Nrf2+DEX prior to modeling on cell viability was assessed using CCK-8 assay.Oncosis characteristics were evaluated using transmission electron microscopy and Annexin V-FITC/PI flow cytometry.The oxidative stress markers(GSH,GSH-Px,MDA,SOD and ROS),mitochondrial membrane potential,energy metabolism,and inflammatory cytokines(TNF-α,IL-6 and IL-1β)in the cells were quantified using standard kits,and the expressions of porimin,caspase-3 and Nrf2 pathway proteins were analyzed using Western blotting and qRT-PCR.Results HS induced typical oncotic features in HSKMCs including organelle swelling and cytoplasmic vacuolization.DEX pretreatment significantly attenuated these changes,reduced Annexin V+/PI+cell ratio and cellular porimin expression,and lowered the levels of ROS and MDA while restoring GSH and SOD levels.DEX pretreatment also significantly increased the mitochondrial membrane potential and ATP level,upregulated the expressions of Nrf2,p-Nrf2,HO-1 and NQO1,and suppressed the expressions of TNF-α,IL-6 and IL-1β.The protective effects of DEX were obviously attenuated by interventions with ML385 or si-Nrf2.Conclusion DEX mitigates HS-induced HSKMC oncosis by activating the Nrf2/HO-1 pathway to relieve oxidative stress,mitochondrial dysfunction,and inflammatory responses.关键词
右美托咪定/横纹肌溶解症/胀亡/人骨骼肌细胞/Nrf2/HO-1通路Key words
dexmedetomidine/rhabdomyolysis/oncosis/human skeletal muscle cells/Nrf2/HO-1 pathway引用本文复制引用
刘洋,贾亿卿,李程程,毛汉丁,刘树元,单毅..右美托咪定通过激活Nrf2/HO-1通路减轻热应激诱导的人骨骼肌细胞胀亡[J].南方医科大学学报,2025,45(3):603-613,11.基金项目
166工程项目(231-CXCY-N101-07-07-01) （231-CXCY-N101-07-07-01）
