Role and Mechanism of Mitochondrial Dynamics in Gastrocnemius Injury Caused by OSAHS Combined with Obesity / 医学研究杂志

ABSTRACT

Objective To explore the effect of chronic intermittent hypoxia(CIH)combined with high-fat diet(HFD)on gastroc-nemius muscle in mice and its possible mechanism.Methods A mouse model of obstructive sleep apnea hypopnea syndrome(OSAHS)combined with obesity was established by simulating CIH and HFD.Mice were divided into normal control group(NC),CIH group,HFD group,and CIH+HFD group.Hematoxylin-eosin(HE)staining was used to observe the structural changes of the gastrocnemius in each group of mice,and adenosine triphosphate(ATP)enzyme staining was used to analyze the changes in the types of muscle fibers in the gastrocnemius.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the mRNA expression level of MHC i-sotype genes(MHC1,MHC2),mitochondrial function related genes(Cs,Ant,NQO1,Hmox1,OGG1)gastrocnemius cells of mice;Western blot was used to detect the expression level of apoptosis-related proteins(cleaved-caspase-3),mitochondrial fusion proteins(Mfn1,Mfn2,OPA1)and mitochondrial division proteins(Drp1 Ser616,Fis1)in gastrocnemius cells of mice.Results Compared with the NC group,the gastrocnemius structure of the mice in the CIH+HFD group was significantly damaged.while the type Ⅰ muscle fibers in the gastrocnemius were decreased,the type Ⅱ muscle fibers in the gastrocnemius were increased.The expression level of MHC1mRNA in the gastrocnemius cells was decreased,and the expression level of MHC2mRNA was increased.In addition,the protein expressions of cleaved-caspase-3,mitochondrial division proteins(Drp1 Ser616 and Fis1)were significantly up-regulated in the CIH+HFD group.The mRNA or protein expressions of Cs,Ant,NQO1,Hmox1,OGG1,Mfn1 were down-regulated.Conclusion CIH combined with HFD can lead to structural and functional damage of gastrocnemius in mice,which may be related to mitochondrial dysfunction caused by mitochondrial dynamics disorder.