| Objective:Chronic obstructive pulmonary disease(COPD)is a chronic respiratory disease characterized by persistent respiratory symptoms and airflow restriction.These symptoms are related to the abnormalities of airway and / or alveoli caused by smoking and environmental exposure.The diaphragm of COPD has dysfunction such as decreased muscle strength.At present,exercise training has been proved to effectively improve the diaphragm dysfunction of COPD mice.However,the effect of different exercise intensity on the diaphragm dysfunction of COPD mice and its possible mechanism are not clear.The increased expression of muscle atrophy F-box protein(Atrogin-1)and muscle-specific RING finger protein 1(MuRF1)can increase muscle protein degradation,which is an important factor of skeletal muscle atrophy,and exercise can regulate the expression of Atrogin-1 and MuRF1 in diaphragm.Therefore,the purpose of this study was to observe the effects of different exercise intensities on the structure and function of the diaphragm in COPD mice,as well as Atrogin-1 and MuRF1,in order to provide a theoretical basis for clinical exercise rehabilitation in COPD patients.Methods:Forty healthy male C57BL/6J mice were randomly divided into blank control group(CG,n = 8),model control group(SG,n = 8),low intensity exercise group(LG,n = 8),medium intensity exercise group(Mg,n = 8)and high intensity exercise group(Hg,n = 8).Among them,the mice in the blank control group were raised in the conventional environment,provided with diet on time,and did not carry out smoke exposure.The model control group,low intensity exercise group,medium intensity exercise group and high intensity exercise group were exposed to cigarette smoke(CS)for 25 weeks.After modeling successfully,the exercise group underwent low intensity exercise(35% maximum speed),medium intensity exercise(55% maximum speed)and high intensity exercise(85% maximum speed)for 9 weeks respectively,and the model control group did not carry out exercise intervention.After the exercise,the diaphragm muscle strength of mice in each group was tested in vitro,and the lung and diaphragm tissues of mice were stained with hematoxylin eosin(HE).The tissue structure was observed,and the number of alveoli and the cross-sectional area of diaphragm fibers were calculated.The expressions of Atrogin-1 and MuRF1 proteins in diaphragm were detected by western blot.Results:(1)HE staining of lung tissueIn the blank control group,the pulmonary alveoli were uniform in size and regular in shape,the structure of alveolar wall and bronchial wall was complete,and the mucosal ciliated columnar epithelium was normal.In the model control group,the alveoli were large and abnormally shaped,with large alveoli fused by multiple small alveoli,thickening of bronchial wall,destruction of mucosal ciliated columnar epithelium,and infiltration of inflammatory cells.Compared with the model control group,the mice in the exercise group had smaller alveoli,more complete alveoli,thinner bronchial tube wall and less damage to mucosal epithelium.(2)Number of alveoliCompared with the blank control group,the number of alveoli in the model control group decreased significantly(P<0.05).Compared with the model control group,the number of alveoli in low intensity exercise group and medium intensity exercise group increased significantly(P<0.05),but there was no significant change in the number of alveoli in high intensity exercise group(P>0.05).(3)HE staining of diaphragm tissueIn the blank control group,the diaphragm fibers were arranged closely and orderly,with complete structure and small cell space.In the model control group,the arrangement of diaphragm fibers was disordered and sparse,muscle fibers atrophied,and some muscle fibers were damaged and broken.Compared with the model control group,the diaphragm structure of the exercise group was improved,and compared with the low intensity and high intensity exercise groups,the diaphragm fibers of the medium intensity exercise group were arranged more closely,the muscle fibers were full and the structure was complete.(4)Diaphragmatic fiber cross-sectional areaThe diaphragmatic fiber cross-sectional area of the model control group was significantly smaller than that of the blank control group,but there was no statistical significance(P>0.05).Compared with the model control group,the diaphragmatic fiber cross-sectional area of mice in the medium intensity group increased significantly(P<0.05).There was no significant difference between the other two groups(P>0.05).(5)Diaphragm functionCompared with the blank control group,the diaphragm muscle strength of the model control group decreased to some extent,but there was no statistical significance(P>0.05).Compared with the model control group and low intensity exercise group,the diaphragm muscle strength of mice in medium intensity exercise group increased significantly(P<0.05).Compared with the model control group,there was no significant difference of the diaphragm muscle strength in low intensity exercise group and high intensity exercise group(P>0.05).(6)Expression levels of Atrogin-1 and MuRF1 in diaphragmCompared with the blank control group,the expression of Atrogin-1 and MuRF1 protein in the diaphragm of mice in the model control group increased to a certain extent,but there was no statistical significance(P>0.05).Compared with the model control group,the expression of Atrogin-1 protein in the diaphragm of mice in the three exercise groups decreased,and the decrease was greater in the medium intensity exercise group,but there was no significant difference in all groups(P>0.05).Compared with the model control group,the expression of MuRF1 protein in the diaphragm of mice in the medium intensity exercise group decreased significantly(P<0.05),and the expression of MuRF1 protein in the diaphragm of mice in the low intensity and high intensity exercise groups decreased,but there was no significant difference(P>0.05).Conclusion:After 9 weeks of exercise intervention,compared with low intensity exercise and high intensity exercise,medium intensity exercise can better improve the structure and function of diaphragm in COPD mice,and has a more prominent effect on reducing the degradation of diaphragm protein in COPD mice. |
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