Peripheral skeletal muscle dysfunction is observed in many patients with chronic obstructive pulmonary disease(COPD).A significant number of patients with normal weight also suffer muscle wasting.Furthermore,some investigators have found an association between reduced muscle mass and survival in COPD patients,independent of a reduction of FEV1.The molecular mechanisms of muscle wasting remains as yet unknown.Our study was to explore the role of ubiquitin-proteasome pathway(UPP) in the loss of muscle mass.
11 consecutive COPD patients(aged 67.7±8.1 years,FEV1 percentage of predicted of 49.6±10.2%) and 6 healthy age-matched control subjects were enrolled in the study.All subjects were underwent 6 minute walk test.Health-related quality of life(HRQL) was measured using St. George’s Respiratory Questionnaire(SGRQ).Whole-body and extremity fat free mass(FFM) were assessed by dual-energy X-ray absorptiometry.Samples of peripheral muscle were collected from the quadriceps by microbiopsy procedure(Bard,USA.).The extent of ubiquitin expression in skeletal muscle was determined by immunohistochemistry.
Whole-body and extremity FFM were significantly lower in the COPD patients than in healthy control(whole body 50.1±8.4kg vs 53.9±10.5kg,p<0.05;extremities 21.4±4.6kg vs 25.2±5.2kg,p<0.01).The intensity of ubiquitin immunostaining in quadriceps muscle fibers in COPD patients was significantly higher than in control(110.1±2.0 density units vs 85.8±0.4 density units,p<0.01).Whole-body FFM was positively correlated with 6 minute walk distance(r=0.63,p<0.05).There was significantly negative correlation between extremity FFM and expression levels of ubiquitin(r=-0.78,p<0.05),SGRQ total score(r=-0.54,p<0.05).
Depletion of FFM is associated with a decline in HRQL and exercise capacity in COPD patients.The ubiquitin expresion levels is up-regulated in these patients.Therefore,the UPP might be involved in peripheral skeletal muscle wasting of COPD patients.
Drug development targeting UPP may provide novel strategies for treating skeletal muscle abnormalities in COPD.
Yi Ming Yuan, None.