Skeletal muscle degradation of chronic obstructive pulmonary disease rats and relationship with interleukin-15

Abstract

Objective To study the relationship of ubiquitin-proteasome pathway (UPP)and interleukin-15 (IL-15) in skeletal muscle degradation of COPD rats,in order to provide scientific theories for prevent increase protein degradation in skeletal muscle of COPD patients.Methods Forty-five healthy adult male SD rats were randomly divided into a COPD model group (n =30)and a normal control group (n =15).The COPD rat model was established by exposure to cigarette smoke and instillation of lipopolysaccharide (LPS).The mRNA and protein levels of E2-14K,MAFbx,Ub in diaphragm,gastrocnemius and intercostal muscle were measured by Real time fluorescence quantitative PCR and Western blot.The concentration of IL-15 and TNF-α in serum,diaphragm,gastrocnemius and intercostal muscle was measured by ELISA.Results The expression of mRNA and protein of E2-14K,MAFbx,Ub compared with the normal control group in diaphragm,gastrocnemius and intercostal muscle were all increased in the COPD model group.The IL-15 and TNF-α level in serum,diaphragm,gastrocnemius and intercostal muscle were higher in the COPD group than the control group.In serum,diaphragm,gastrocnemius and intercostal muscle,the level of IL-15 was positively correlated with TNF α(serum r =0.75,diaphragm r =0.81,gastrocnemius r =0.82,intercostal muscle r =0.78,P ＜0.05).The level of IL-15 in diaphragm,gastrocnemius and intercostal muscle was positively correlated with the expression of E2-14K,MAFbx,Ub (diaphragm r =0.88,r =0.86,r =0.87;gastrocnemius r =0.85,r =0.87,r =0.76 ;intercostal muscle r =0.85,r =0.80,r =0.84,P ＜ 0.05).The level of IL-15 in diaphragm,gastrocnemius and intercostal muscle was negatively correlated with the body weight net growth of rats after COPD models were established (diaphragm r =-0.90,gastrocnemius r =-0.85,intercostal muscle r =-0.82,r =-0.82,P ＜0.05).Conclusions In COPD rats,IL-15 may in company with TNF-αcontribute to impat skeletal muscle degradation through the ubiquitin proteasome pathway. Key words: Chronic obstructive pulmonary disease; Ubiquitin-proteasome pathway; Interleukin-15; Tumor necrosis factor-α