Effects Of Moderate-intensity Exercise On PPARγ And Inflammation Of Diaphragm In COPD Mice

Objective Chronic obstructive pulmonary disease(COPD),accompanying inflammation caused by sensitivity to harmful particles or gas,is characterized by persistent and progressive airflow limitation.Pulmonary muscle dysfunction is one of the extrapulmonary symptoms of COPD.The diaphragm is the most important affected inspiratory muscle,and inflammation may play a vital role in the advent and development of diaphragm dysfunction.Moderate-intensity aerobic exercise is an effective way to alleviate inflammation and has been widely used in pulmonary rehabilitation,and it is a potential method for reducing diaphragm inflammation due to COPD and attenuating diaphragm dysfunction.However,the mechanism is unclear.PPARγ is involved in the pathophysiological process of COPD and can relieve inflammation.In addition,it can be regulated by exercise.Hence,PPARγ is a potential target by which exercise alleviates diaphragm inflammation and dysfunction caused by COPD.We established COPD model mice,investigated the effect of regular moderate-intensity aerobic exercise on COPD diaphragm inflammation and dysfunction,and observed the role of PPARγ.MethodsTwenty-four 8-week healthy male C57BL/6J mice were randomly and equally divided into control,model,and exercise groups.The mice of the model and exercise groups underwent 25 weeks of progressive cigarette smoke exposure for the establishment of COPD models.The control group received no intervention.The exercise group performed 9-week moderate-intensity aerobic exercise on a treadmill.After the exercise intervention,the lungs and diaphragms were dissected and stained with hematoxylin and eosin(HE).The average alveolar areas and mean linear intercept of the lungs and cross-sectional areas(CSAs)of the diaphragms were calculated through histological analysis.Western blot was used in detecting the protein levels of PPARγ,TNF-α,IL-6,and IL-1β in the diaphragm.Results(1)No obvious histological alteration in HE-stained lung tissues was observed in the control group.The COPD model group showed evident alveolar structure disorders and bronchial wall thickness.This kind of alteration was relieved in the COPD exercise group.The average alveolar CSA of the COPD model group was significantly increased compared with that in the control group(p < 0.01).Nine-week moderate-intensity aerobic exercise decreased the average alveolar CSA compared with that in the COPD model group(p < 0.05).The mean linear intercept of the COPD model group increased compared with the control group and decreased by exercise,but no significant change was observed.(2)The HE staining of the diaphragm showed that the muscle fibers of the control group showed no changes.The intermuscular septum of the diaphragm muscle fibers of COPD model group widened,and the nuclei were not densely arranged.The CSAs of the diaphragm muscle fibers of the COPD exercise group increased compared with those in the COPD model group(p < 0.05).The CSAs of the diaphragms of the COPD model group were smaller than those in the control group.(3)The PPARγ protein levels in the diaphragms of the COPD model group decreased compared with those in the control group(p < 0.05).Compared with COPD model group,the COPD exercise group showed significant increase in PPARγ protein level(p< 0.01).(4)The TNF-α,IL-6,and IL-1β levels in the diaphragms of the COPD model group increased.TNF-α showed significant increase(p < 0.01).Nine-week exercise decreased TNF-α,IL-6,and IL-1β levels in the diaphragms in the COPD exercise group,but the increases were not significant compared with those in the COPD model group.ConclusionModerate-intensity aerobic exercise considerably alleviated pathologic injuries of diaphragm.Lowered degree of inflammation may be associated with increase in PPARγlevel in COPD-affected diaphragm.