Establishment And Evaluation Of A COPD Rat Model With Skeletal Muscle Atrophy

ObjectiveSkeletal muscle atrophy in chronic obstructive pulmonary disease(COPD)seriously affects the exercise ability and quality of life of COPD patients.In order to study the mechanism of COPD skeletal muscle atrophy,it is necessary to establish a related animal model.However,no COPD animal model of skeletal muscle atrophy has been established at home and abroad.Therefore,the COPD rat model was established by simple smoking exposure,and on this basis,the successful establishment of COPD animal model of skeletal muscle atrophy by simple smoking exposure was evaluated.MethodThirty-five 8-week-old male SD rats were randomly divided into COPD model group and control group,including 20 rats in the model group and 15 rats in the control group.The rats in the model group were exposed to cigarette smoke for 4 months to establish COPD model,while the rats in the control group were routinely raised without any intervention.During the period,the body weight and tensile force of rats were measured every month.Four months later,8 rats were extracted from the model group and 7 rats from the control group.The rest of the rats were raised normally in order to improve the method and prolong the modeling cycle after the failure of modeling.The rats in the two groups were killed and the blood was taken from the abdominal aorta.Airway alveolar perfusion was performed in rats.The middle lobe of the right lung,the diaphragm and the right gastrocnemius muscle were removed.Then the pathological observation of lung tissue,diaphragm and gastrocnemius muscle was carried out by HE staining,and the alveolar cross-sectional area of rats was calculated at the same time.The expression of inflammatory factors in alveolar lavage fluid and serum was detected by ELISA.The expression of E3 ligase muscle atrophy related gene-1(atrogin-1)and muscle-specific cyclic finger protein-1(MuRF-1)in diaphragm and gastrocnemius muscle were detected by Western blot.Results1.Four months after cigarette smoking,the lung tissue of the model group showed COPD characteristics: inflammatory cell infiltration,narrow airway section,more mucus in the airway,rupture and fusion of alveoli.The alveolar cross-sectional area was significantly larger than that of the normal control group(P < 0.01),and the inflammatory level of alveolar lavage fluid was significantly higher than that of the control group(P < 0.01).The expression level of BALF inflammation in airway was normal.2.Four months after exposure,the rats in the model group showed the characteristics of COPD skeletal muscle atrophy: the body weight of the model group was significantly lower than that of the control group(P < 0 01),and the tensile force of the model group was significantly lower than that of the control group(P < 0 01).In the model group,the muscle fibers of diaphragm tissue were reduced and the muscle nuclei were disordered.The septum of muscle fibers increased,interstitial fibers increased and blood vessels and capillaries proliferated,while in the control group,the diaphragm fibers were full and tightly arranged,and there was no interstitial hyperplasia.The structure of muscle fibers in the model group was disordered,some muscle fibers were twisted,the arrangement of muscle fibers was slightly sparse compared with the control group,there was an increase in interstitial fibers,the gastrocnemius muscle fibers in the control group were arranged in a close and orderly manner,and the interval was normal.3.The expression of protein degradation factor Atrogin-1 and MuRF-1 in diaphragm and gastrocnemius muscle of the model group was significantly higher than that of the control group(P < 0.01),which was significantly higher than that of the control group(P < 0.01),which was significantly higher than that of the control group(P < 0.01).4.The expression of serum inflammatory factors IL-6,IL-8 and TNF-? in the model group was significantly higher than that in the control group(P < 0.01),and the expression of serum inflammatory factors in the model group was significantly higher than that in the control group(P < 0.01).ConclusionsSmoking exposure alone led to the characteristics of COPD disease in rats.At the same time,the systemic inflammatory response,sparse arrangement of muscle fibers,decreased tension and the expression of proteolytic factors in skeletal muscle tissue were significantly increased.The results showed that the COPD rat model of skeletal muscle atrophy was successfully established by smoking exposure alone.