Objective:To investigate whether the 25-week incremental smoke exposure can successfully establish a mouse model of skeletal muscle dysfunction in chronic obstructive pulmonary disease(COPD).Method:Healthy male C57BL/6 mice were randomly divided into the model group(MG,n=6)and the con-trol group(CG,n=6).The MG mice were whole-body exposed to cigarette smoke 6 days/week for 25 weeks,with 4h intervals between sessions.The number of lighted cigarettes and the daily frequency of ciga-rette smoking were gradually increased throughout the experiment.The CG mice were routinely housed.During the modeling,the body weight of the mice was measured monthly,and the grip strength was measured bi-monthly.Lung function tests and isolated gastrocnemius strength were performed at the end of the 25-week smoke exposure.Pathological changes in lung and gastrocnemius were observed by HE staining.Alveolar cross-sectional area(CSA),alveolar mean linear intercept(MLI),and myofiber CSA were calculated.Western Blot was performed to detect the expression of MyHC(slow),MyHC(IID),Atrogin-1,and MuRF-1 in the gas-trocnemius.Result:Compared with CG mice:①MG mice showed significant general condition change and significant re-duction in body weight(P＜0.05);②MG mice showed typical changes of chronic bronchitis and emphysema in lung tissue,with significant increase in alveolar CSA and MLI(P＜0.05),and significant reduction in lung function including FVC,FEV20,MV,PEF and Cydn(P＜0.05);③MG mice showed increased spacing be-tween muscle fibers,significantly reduced CSA(P＜0.05),decreased expression of MyHC(slow)(P＜0.01),and reduced grip strength(P＜0.05),as were isometric contraction strength and force during 35 Hz electrical stimula-tion of the gastrocnemius muscle(P＜0.05);④The expression levels of Atrogin-1 and MuRF-1 in the gastroc-nemius were elevated in MG mice(P＜0.05).Conclusion:Long-term incremental smoke exposure led to obvious characteristics of COPD in mice,with de-creased skeletal muscle contractile function,promoted muscle fiber type transformation and muscle atrophy,and elevated the expression level of muscle atrophy-related proteins.This suggests that 25 weeks of incremen-tal smoke exposure could successfully establish a mouse model of COPD skeletal muscle dysfunction.
维普
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