Effects Of Resistance Exercise On Oxidative Stress And Nrf2 Pathway In Skeletal Muscle Of COPD Rats

ObjectiveChronic Obstructive Pulmonary Disease(COPD)is a kind of common Chronic respiratory Disease in middle-aged and elderly people.However,patients are often accompanied by a series of extrapulmonary complications,especially the occurrence of skeletal muscle dysfunction.The clinical manifestation is the decrease of muscle strength and endurance,which seriously affects the quality of life of patients.The occurrence of skeletal muscle oxidative stress caused by smoking,inflammation and other internal and external factors in COPD patients is one of the important reasons for the decline of skeletal muscle function in COPD patients.At present,resistance exercise has been recommended to be used in pulmonary rehabilitation of COPD due to its outstanding effect of improving skeletal muscle mass and strength,and exercise has a certain regulatory effect on oxidative stress,but the specific mechanism is not clear.Keap1-Nrf2/ARE pathways as an important antioxidant pathways in the human body,can promote the downstream of antioxidant enzymes and Ⅱ detoxifying enzyme gene(such as SOD,NQO1,HO-1)transcription,give play to the role of protection for the body,may participate in the improvement of patients with COPD skeletal muscle oxidative stress resistance movement mechanism.Therefore,the purpose of this study was to observe the effects of resistance exercise on the oxidative stress and Nrf2 pathway of skeletal muscle in smoking-induced COPD rats,and to explore the possible molecular mechanism of exercise in improving skeletal muscle dysfunction in COPD rats.MethodIn this study,16 healthy male SD rats were exposed to cigarette smoke for 16 weeks to establish a model of skeletal muscle dysfunction in COPD rats.After the successful establishment of the model,COPD rats were randomly divided into COPD control group(CG,n=8)and resistance exercise group(RT,n=8).The resistance exercise group received load-bearing ladder exercise for 9 weeks,and the COPD control group received standardized feeding without any exercise intervention.After the exercise,the body weight and tensile strength of the rats were measured.The morphological structure of the skeletal muscle of the rectus femoris muscle of the rats was observed by hematoxylin-eosin staining(HE),and the cross-sectional area of muscle fiber(CSA)was calculated.The content of MDA in skeletal muscle of rats was measured by biochemical method.The expression levels of Nrf2,Keap1 and antioxidant proteins SOD1,HO-1 and NQO1 in the skeletal muscle of the rats were detected by Western blot.Results1.Compared with COPD control group,9 weeks of resistance exercise significantly increased the grip strength of rats(P < 0.01).2.The transverse section of HE staining showed that the rectus femoris muscle in COPD control group was loose and disordered in structure,with significantly widened intercellular space,reduced nuclear number,different muscle fiber sizes,and increased intercellular stitium and capillaries.However,in the resistance exercise group,the fibers of the rectus femoris muscle were tightly arranged and regular,the intercellular space was significantly narrowed,and the nuclear density and cell number were significantly increased.Meanwhile,compared with COPD control group,resistance exercise for 9 weeks significantly increased the crosssectional area of rectus femoris fibers in COPD rats(P < 0.05).3.Compared with COPD control group,MDA content in skeletal muscle in resistance exercise group was significantly decreased(P < 0.05).4.Compared with COPD control group,Nrf2 protein expression was significantly increased in resistance exercise group(P < 0.05).The expression of Keap1 protein was significantly decreased(P < 0.01).5.Compared with COPD control group,the expression of antioxidant protein SOD1 in skeletal muscle of the resistance exercise group was significantly increased(P < 0.01),but the expression of HO-1 and NQO1 was not increased.ConclusionsResistance exercise can significantly improve the muscle strength of skeletal muscle in COPD rats,improve the abnormality of skeletal muscle morphology and structure,and improve the atrophy and dysfunction of skeletal muscle in COPD patients.Resistance exercise improves oxidative damage of skeletal muscle in COPD rats,which may be related to the increase of the expression of some antioxidant enzymes,such as SOD1,by inducing the activation of Nrf2 mediated antioxidant pathway and enhancing the antioxidant capacity of skeletal muscle.