Salidroside Improves Skeletal Muscle Atrophy In COPD Rats Through The MSTN/Activin Pathway

Objective: To explore whether salidroside can improve skeletal muscle atrophy in COPD rats through the MSTN/ activin pathway.Methods: Thirty-six male SD rats were divided into control group(n = 9)and COPD model group(n = 27).The COPD model was established by passive smoking in the COPD model group,and the blank model was established by routine air inhalation in the control group.After 4 months of passive smoking,3 rats were randomly selected from the control group and the model group for pulmonary function and histopathology examination,respectively,to evaluate the COPD model.The remaining COPD model rats were randomly divided into 4 groups: smoking cessation group(6 rats): COPD model group + placebo;Smoking cessation + intervention group(6 rats): COPD model group rats +salidroside intervention;Continuous smoking group(6 rats): COPD model group + smoking + placebo;Continuous smoking + intervention group(6 rats): COPD model group rats + smoking + salidroside intervention.Rats in control group(6 rats)were given placebo by gavage.Placebo was given 1ml/100 g saline gavage twice a day for 2months.Salidroside intervention was administered by gavage at a concentration of 25mg/ml and a dose of 1ml/100 g each time,twice a day for 2 months.Two months later,the experimental animals were weighed and killed.Quadriceps femoris muscle weight,visceral body ratio,muscle fiber cross-sectional area,skeletal muscle histomathology and the proportion of type I(oxidative type)muscle fiber were detected.The protein levels of MSTN、Act RIIB、Act RIIA、ALK4、ALK5and Smad3 were detected by WB method.The m RNA levels of MSTN、Act RIIB、Act RIIA、ALK4、ALK5and Smad3 were detected by RT-PCR.Results:(1)Establishment of COPD rat model: FVC,MMEF,PIF,PEF and MV in COPD model group were significantly decreased compared with control group,with statistical significance(P<0.05).In the pathological section of lung tissue,the infiltration of inflammatory cells was increased compared with that of normal rats.The bronchial epithelial cells were irregular and partly detached,the airway wall was thickened,the columnar ciliated epithelium was collapsed,missing and adhesion,and the alveolar structure was disorder.(2)Tissue morphology and cross sectional area of muscle fiber of rat quadriceps femoris muscle: Stains of the quadriceps femoris muscle tissue in the blank group showed normal structure and compact and orderly arrangement of fibers,while the fibers in the smoking cessation group became slightly separated and disorderly,with more blood vessels and capillaries proliferating.After salidroside intervention,the muscle fibers were small and arranged in a little order.(3)Quadriceps femoris weight and visceral body ratio changes:Quadriceps femoris weight of the smoking cessation group was less than that of the blank group.Quadriceps femoris weight of the smoking cessation group increased compared with that of the smoking cessation intervention group,and that of the continuous smoking + intervention group.Quadriceps femoris muscle weight increased in the smoking cessation group compared with the smoking cessation + intervention group and the smoking cessation + intervention group.The difference between the two groups was statistically significant(P < 0.05).Quadriceps femoris viscera ratio in the smoking cessation group was less than that in the blank group.The quadriceps femoris viscera ratio in the intervention group increased compared with that in the smoking cessation + intervention group and the continuous smoking + intervention group.Quadriceps femoris visceral body ratio of smoking cessation group was increased compared with smoking cessation group and smoking cessation + intervention group.The difference between the two groups was statistically significant(P < 0.05).(4)Proportion of type I muscle fiber in each group:Compared with the blank group,the proportion of type I muscle fiber in the non-smoking group was higher than that in the non-smoking group.The proportion of type I muscle fiber in smoking cessation group and smoking cessation +intervention group was higher than that in smoking cessation +intervention group.The difference between the two groups was statistically significant(P < 0.05).(5)Expression levels of MSTN/ activin pathway genes in each group:he protein and m RNA expression levels of MSTN,Act RIIB,Act RIIA,ALK4,ALK5,Smad3 in smoking cessation group were increased compared with blank group(P < 0.05),The protein and m RNA expression levels of MSTN,ALK4,Smad3 in the intervention group decreased compared with the smoking cessation + intervention group(P <0.05),the m RNA expression levels of Act RIIB and ALK5 were decreased with statistical significance,the protein levels of Act RIIB and ALK5 and the m RNA expression levels of Act RIIA were decreased,but there was no statistically significant difference.Persistent smoking group compared with persistent smoking + intervention group,intervention group MSTN,Act RIIB,Act RIIA,ALK4,ALK5 and Smad3 protein and m RNA expression level decreased,quit smoking group and persistent smoking,smoking + intervention group compared with persistent smoking +intervention group,quit smoking rats a persistent smoking rats MSTN,Act RIIB,Act RIIA,ALK4,ALK5,Smad3 protein and m RNA expression levels(P < 0.05).Conclusion:Salidroside can improve skeletal muscle atrophy in smoking COPD rats by down-regulating the MSTN/ activin signaling pathway.It has a synergistic effect with smoking cessation.