Bu-fei Jian-pi Granules Improve Skeletal Muscle Dysfunction In Copd Rats Via Regulating NF-κb-ubiquitin-proteasomes Signaling

ObjectiveTo evaluate the efficacy of Bu-fei Jian-Pi granules on skeletal muscl edysfuncti on in (chronic obstructive pulmonary disease, COPD) rats, and explore themechanisms via regulating nuclear factor (NF)-κB-ubiquitin (Ub)-proteasomessignaling and provide the basis for clinical application.MethodsSpecific pathogen free (SPF) level72sprague dawley (SD) rats wererandomly divided into control, model, Bu-fei Jian-Pi, PDTC, Bu-feiJian-Pi+PDTC (her einafter referred to as the "combined group") andaminophylline groups, with12rats in each group. The stable COPD ratmodel was duplicated by cigarette smoke inhalations and r epeated bacterialinfections. From the9th to20th week, the rats were admi nistrated withnor mal saline (in control and model groups), Bu-Fei Jian-Pi granule (Bu-FeiJian-Pi group), PDTC (PDTC group), Bu-Fei Jian-Pi granule (combinedgroup) and aminophyline (ami nophyline group). Ani mals were sacrificed atthe20th week. Lung function (VT, PEF, EF50) were measured monthly. Thepathological changes and ultrastructure were observed in biceps, quadriceps,soleus, intercostals muscle tissues of rats. The tension of bi ceps, quadriceps,soleus, intercostals muscle tissues of rats were detected by using thethree-dimensional tissue perfusion syste m. ELISA was used to detect thecontent of Ub in the quadriceps muscle tissues. Polymerase Chain Reaction(PCR) technology was used to detect the gene expressions of tumor necrosisfactor alpha (TNF-α) and nuclear factor kappa B (NF-κB) in the quadricepsmuscle tissues. Results1General statusCompared with the control group, rats in model group were e maciated,listless, less active, less food and water intake. These changes wereimproved in Bu-fei Jian-Pi, PDTC, combined and aminophylline group wereimproved, especially in Bu-fei Jian-Pi and combined group. Compared tocontrol group, body weight gain was l ower in model group. While it wasimproved in Bu-fei Jian-Pi, combined and aminophylline group from13t hweek. But there was no signifi cant statistical diffe rence (P>0.05).2Lung functionThe VTof the COPD rats in the model group was lower compared withcontrol group since the8t hwe ek (P<0.01). PEF and EF50wer e reduced since4t hweek(P<0.01). VT, PEF and EF50in combined group were higher than thatin model group since the16t hweek (P<0.05). PEE was higher in Bu-fe iJian-Pi group than that in model group since16t hweek (P<0.05). EF50washigher in combined group than PDTC group since16t hweek (P<0.05). At the20t hweek, VT, PEF, EF50in Bu-fei Jian-Pi and combined gr oup were higherthan model group (P<0.05or P<0.01).3Skeletal muscle tissue pathology and ultrastructureMarked pathology and ultrastructure impair ment was observed inskeletal muscle in rats with COPD, and it was improved i n Bu-fei Jian-Pi,combined group, PDTC, and a minophylline group, espe cially in Bu-fe iJian-Pi and combined group.4Skeletal muscle tentionThe tension in the biceps, quadriceps, soleus, intercostals muscletissues declined in rats in model group compared with control group (P<0.01).The tension of qua driceps was improved in Bu-fei Jian-Pi, combined andmi nophylline group compared to model group (P<0.01). The tension of biceps,soleus, intercostals muscle tissues was i mproved in Bu-fei Jian-Pi andcombined group compared wi th model group (P<0.01). The tension of biceps,quadriceps, intercostals muscle was elevated in Bu-fei Jian-Pi andcombined group than aminophylline group (P<0.05or P<0.01). The tension ofquadriceps and soleus was hi gher in combined gr oup than that in PDTC andaminophylline group (P<0.05or P<0.01). There was no statistical difference between ami nophylline and PDTC group (P>0.05).5Genes and proteins expression involved in NF-κB-ubiquitin(Ub)-proteasomes signaling in quadriceps tissueThe expression of Ub, TNF-α mRNA, NF-κBp65mRNA in quadriceps weresignificantly higher in model group than control group (P<0.01). Ub, TNF-αmRNA, NF-κBp65mRNA in Bu-fei Jian-Pi and combined group wer esignificantly lower than model group (P<0.01). Ub in ami nophylline andPDTC group were significantly lower than mode l group (P<0.01). NF-κBp65mRNA in Bu-fei Jian-Pi, combined and PDTC group were significantly lowe rthan aminophylline group (P<0.01). Ub, TNF-α mRNA in ami nophylline andPDTC group were significantly higher than Bu-fei Jian-Pi and combinedgroup (P<0.05or P<0.01). NF-κBp65mRNA in combi ned and PDTC group weresignificantly lower than Bu-fei Jian-Pi group (P<0.01). There was nostatistical di fference between aminophylline and PDTC group in Ub andTNF-α mRNA (P>0.05), the same to NF-κBp65mRNA in c ombined a nd PDTC group(P>0.05).Conclusion1Bu-fei Jian-Pi granules can obviously i mprove skeletal muscledysfuncti on and general condition, lung funct ion, skeletal muscle tissuepathological damage and skeletal muscle tension in rats with COPD, showmore benefit than PDTC and Aminophylline.2NF-κB-ubiquitin(Ub)-proteasomes si gnaling mi ght be involved in themechanism of Bu-fei Jian-Pi granules, which can reduce muscle proteinbreakdown, promot e protein synthesis.