阻塞性睡眠呼吸暂停低通气综合征合并肥胖通过内质网应激加剧小鼠腓肠肌损伤OA

Objective:To explore the effects of obstructive sleep apnea hypopnea syndrome(OSAHS)combined with obesity on the gastrocnemius muscle in mice and its possible mechanism.Methods:Forty male C57BL/6 mice(6-8 weeks,25-30 g)were randomly and evenly divided into 4 groups,with 10 mice in each group:control group(untreated),CIH group(intermittent hypoxia),high-fat diet(HFD)group(fed with HFD),CIH+HFD group(intermittent hypoxia with HFD).After 14 weeks,the gastrocnemius muscle tissues of the mice were collected.HE staining was used to observe the morphological changes of the gastrocnemius muscle.Western blotting was performed to detect the expression of skeletal muscle fiber types,myocyte generation and differentiation,endoplasmic reticulum stress(ERS),inflammatory factors,and apoptosis-related proteins in the gastrocnemius muscle tissues.Real-time fluorescence quantitative PCR was used to detect the relative mRNA expression levels of skeletal muscle fiber types,myotube formation and ERS.C2C12 myotubes were induced with different concentrations of sodium palmitate(PA),and the formation of lipid droplets was observed by Oil Red O staining.C2C12 myotubes were divided into the control group(untreated),CIH group(intermittent hypoxia),PA group(200 μmol/L PA),and CIH+PA group(200 μmol/L PA combined with intermittent hypoxia).After 5 days,morphological changes were observed under an optical microscope.Western blotting was used to detect the expression of skeletal muscle fiber types,myogenesis,endoplasmic reticulum stress,inflammatory factors,and apoptosis-related proteins.Results:Compared with the control group,the gastrocnemius muscle fibers of mice in CIH+HFD group were significantly damaged,with a significant decrease in the relative expression of MYHC7 protein and MYHC ⅠmRNA(P<0.01),and a significant increase in the expression of MYHCⅡx protein and mRNA(P<0.05);the expression of MYOG,MYOD1 protein and MYOG,MYOD mRNA decreased significantly(P<0.01);the expression of IRE1α,XBP1s and CHOP protein and mRNA increased greatly(P<0.05);the expression of Caspase-3,TNF-α and IL-6 protein increased markedly(P<0.05).Compared with the control group,the structure of C2C12 myotubes in CIH+PA group was damaged,with a significant decrease in MYHC7,MYOG,MYOD1 protein and Bcl-2 protein(P<0.01 or P<0.05),and a significant increase in MYHCⅡx protein,GRP78,CHOP,IRE1α,XBP1s protein and IL-6,Caspase-3,Bax protein(P<0.05 or P<0.01).Conclusion:OSAHS combined with obesity may induce damage to the gastrocnemius muscle in mice by activating ERS-mediated apoptosis pathways,while also causing a shift in gastrocnemius muscle fiber from type Ⅰ to type Ⅱ,thereby inhibiting muscle formation and differentiation.