Objective To explore the action of Bufei Jianpi formula(BJF)on mitochondrial damage to skeletal muscle in chronic obstructive pulmonary disease(COPD)rats via its regulation of the IRS-1/PI3K signaling axis.Methods 60 SPF SD rats were randomly divided into Control group,Model group(COPD stable stage group),aminophylline(Am)group,BJF group,pioglitazone(PIO)group and BJF+PIO group,with 10 rats per group.A stable COPD rat model was established via forced smoking and Klebsiella pneumoniae nasal drip method.Samples were taken from the 9th week to the end of the 20th week,and the weight of the rats was measured every week.Routine sectioning and HE staining were performed on lung and skeletal muscle tissue,and corresponding pathological changes were observed under a light microscope.The lung function of the rats was observed by whole-body plethysmography in weeks 0,8,and 20,including tidal VT,PEF,and EF50.The mRNA expression of IRS-1,leptin,PGC1-α,and PI3K in rat skeletal muscle was detected by qPCR.The expression of PGC-1α,TFAM,IRS-1,PI3K,AKT,p-AKT,and leptin in rat skeletal muscle tissue was detected by Western blot.Results The Model group,but not the Control group,showed a large number of inflammatory cells infiltrating the alveolar interstitium and bronchus,indicative of lung disease;some alveolar walls had broken and fused to form air cavities,and fiber networks were destroyed.After drug treatment,the rats showed improved alveolar wall and fiber network integrity and reduced inflammatory cell infiltration in the bronchus,especially those in the BJF and Am groups.In the drug treatment groups,the skeletal muscle pathology of each group showed improved spatial arrangement,the atrophy and fracturing of muscle fibers were ameliorated to different degrees,and cytoplasmic staining of muscle cells was uneven,and the BJF group showed the most significant effects.Compared with the Control group,the Model group's PEF,VT,and EF50 significantly decreased from week 8(P＜0.01),while the BJF,BJF+PIO and Am groups had significantly increased PEF and EF50(P＜0.01).Compared with Control group,the Model group's mRNA and protein expression levels of IRS-1,PGC-1α,and PI3K were significantly decreased(P＜0.05,P＜0.01),the level of leptin was significantly increased(P＜0.01).Compared with the Model group,the mRNA and protein expressions of IRS-1,PGC-1α and PI3K in the BJF group were significantly increased(P＜0.05,P＜0.01),and the mRNA expression of IRS-1 in the PIO group was significantly increased(P＜0.01).The BJF+PIO group's mRNA levels of PGC-1α(P＜0.01)and mRNA and protein levels of IRS-1 and PI3K were significantly increased(P＜0.05,P＜0.01).The mRNA and protein expression levels of PI3K in the Am group were significantly increased(P＜0.01).The expression levels of leptin mRNA were significantly decreased in the four treatment groups(P＜0.01),and the expression of leptin protein was significantly decreased in all treatment groups except the Am group(P＜0.01).Compared with the Control group,the Model group's quadriceps femoris tissue showed a significant decrease in TFAM and p-AKT expression.TFAM and p-AKT expression in all the treatment groups showed an increasing trend,but the difference was not statistically significant(P＞0.05).Conclusions By regulating the IRS-1/PI3K signaling axis,Bufei Jiempi reduces mitochondrial damage to skeletal muscle,increases the expression of PGC-1α and mitochondrial transcription factor TFAM,enhances mitochondrial biosynthesis,and reduces pathological damage to lung and skeletal muscle tissue.