Influence Of Indomethacin On Skeletal Muscle Protein Catabolism In COPD Malnutrition Rats

Objective:To observe the influence of indomethacin on skeletal muscle protein catabolism and the changes of tumor necrosis factor(TNF) -alpha in COPD malnutrition rats.Methods:100 healthy male adult Wistar rats were randomly divided into two groups:model group(n=80) and normal control group(n=20). Model group was performed with intratracheal instillation of porcine pancreatic elastase and exposed to cigarette smoke to establish COPD models.On the 68th day of modeling,malnutrition was defined if the body weights of the rats in the model group were lower than 90%of the mean body weight of the control group.Model rats were divided into two groups:the non-malnutrition COPD group(n=37) and the malnutrition COPD group(n=40).The malnutrition group rats were divided by randomized block design into four groups(group A,B,C,D).Isotonic physiologic saline was administered to group A,the control group and the non-malnutrition COPD group,and different doses of oral indomethacin were administered to groups B,C,and D daily(group B:IND 0.5mg/kg.d,C:IND 1mg/kg.d,D:IND 2mg/kg.d).After 14 days of intervention,they were changed to normal feeding for 14 days,and then the weights of each rat body were scaled.The concentrations of TNF-αlpha in the serum,the diaphragm and extensor digitorum longus muscle homogenates from these rats were measured by double-antibody sandwiched ABC-ELISA method.The contents of 3-methyl-histidine and tyrosine in the diaphragm and extensor digitorum longus muscle homogenates were detected by high-performance liquid chromatography.Results:(1) The body weight growth rate of the intervention group C rats was significantly higher than the intervention groupB,D and A (P=0.001,P=0.002,P=0.00),and compared with the normal control group and the non-malnutrition COPD group respectively,the difference is not significant(P＞0.05).There was no significant difference between the intervention groups B and D(P＞0.05).The body weight growth rates of the intervention groups B and D rats were slightly higher than the intervention group A,with no significant difference(P＞0.05);they were lower than the non-malnutrition COPD group and the control group with significant difference(P＜0.05,P＜0.01).(2) Before the intervention,the TNF-αlpha concentrations of the serum and the skeletal muscle homogenate of rats of the intervention groups A,B,C and D were significantly higher than those of normal nutrition COPD group(P＜0.01) and the control group(P＜0.01).The COPD normal nutrition group was obviously higher than the control group(P＜0.01).The TNF-αconcentrations of the serum and the skeletal muscle homogenate of rats of the intervention groups B,C andD after the intervention were significantly lower than before the intervention (P＜0.01),and were significantly lower than the intervention group A(P＜0.01),the most significant is the intervention group C.(3) The serum TNF-αlpha concentration and body weight of model group rats were negatively correlated(R=-0.846,P＜0.01),as well as the diaphragm and extensor digitorum longus muscle weights(R=-0.778, P＜0.01;R=-0.772,P＜0.01).(4) The 3-methyl-histidine and tyrosine levels of the diaphragm and extensor digitorum longus muscles of the intervention group A rats were significantly higher the control group(P＜0.01),the normal nutrition COPD group(P＜0.01),and the intervention groups B,C and D(P＜0.01). The COPD normal nutrition group was higher than the control group obviously(P＜0.01).The intervention group C was lower than the COPD normal nutrition group obviously(P＜0.05),as well as the intervention groups B and D.There was no significant difference between the intervention groups B and D(P＞0.05).Conclusion:(1) TNF-αlpha is involved in the occurrence of COPD malnutrition and skeletal muscle amyotrophy.(2) Dose of 1mg/kg indomethacin can reduce the TNF-αlpha levels in the serum and the skeletal muscle homogenate in malnutrition COPD rats,and reduce the catabolic rate of the skeletal muscle proteins in malnutrition COPD rats, which can improve partly the malnutrition COPD rats nutrition and reverse the skeletal muscle atrophy.(3) Dose of 0.5mg/kg or 2mg/kg indomethacin does not have a more remarkable function.