The influence of indomethacin on TNFα and skeletal muscle protein catabolism in chronic obstructive pulmonary disease rat model / 中华内科杂志

ABSTRACT

Objective To observe the influence of tumor necrosis factor-alpha(TNFα) on skeletal muscle protein catabolism in rats with chronic obstructive pulmonary disease (COPD) and the effects of indomethacin (IND) on it. Methods Duplicated COPD model rats were divided into two groups the malnutrition group and the normal nutrition group. The malnutrition group were further divided by randomized block design into four groups. Isotonic physiologic saline was administered to group A, the control and the normal nutrition group, and different doses of oral IND were administered to groups B, C, and D weight, concentrations of TNFα, contents of 3-methyl-histidine ( 3- M H ) and tyrosine (Tyr) in the diaphragm and extensor digitorum longus muscle homogenates were measured before and after the intervention. Results Before the intervention, the concentrations of TNFα in the serum of malnutrition groups were all significantly higher than those of normal nutrition group and the control group. After the intervention (1) The concentrations of TNFα in the serum of the rats of group B, C and D were significantly lower than the group A, especially in group C. The levels of TNFα in serum 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 ). (2) The levels of 3-methyl-histidine in the diaphragm and extensor digitorum longus muscles of the intervention group C was lower than the COPD normal nutrition group, as well as the intervention groups B and D. The contents of tyrosine in the diaphragm and extensor digitorum longus muscles of the intervention group C was lower than that of the COPD normal nutrition group,as well as the groups B and D. The body weight growth value of the intervention group B were slightly higher than the group A, without significant difference( P ＞ 0. 05 ), while the group C was significantly higher than the group A ( P ＜ 0. 01 ). Conclusions TNFα is involved in the occurrence of COPD malnutrition and skeletal muscle amyotrophy. IND can reduce the TNFα levels in the serum and the catabolic rates of the skeletal muscle proteins in malnutrition rats with COPD, so as to improve partly the skeletal muscle atrophy.