[Effects of tumor necrosis factor alpha on proteolysis of respiratory muscles in rats with chronic obstructive pulmonary disease].
OBJECTIVE
To investigate the impact of tumor necrosis factor alpha (TNF-alpha) on proteolysis of respiratory muscles in rats with chronic obstructive pulmonary disease (COPD).


METHODS
Ninety healthy male adult Wistar rats were randomly divided into two groups: a normal control group (n = 20) and a model group (n = 70). The COPD rat model was established by intratracheal instillation of porcine pancreatic elastase and exposure to cigarette smoke for 60 days. Malnutrition was defined as the weight of the rats in the model group lower than 90% of the mean body weight of the control group. Two weeks after the establishment of the COPD model, 10 rats were randomly chosen in the malnutrition group, and received 4 days' therapy of intravenous injection of TNF-alpha monoclonal antibody (McAb) 0.1 mg/kg. The concentrations of TNF-alpha in the homogenates of respiratory muscles were measured by ELISA, and the contents of 3-methylhistidine, tyrosine in homogenates of respiratory muscle were measured by high performance liquid chromatography.


RESULTS
The levels of TNF-alpha in the homogenates of diaphragmatic muscle of the malnutrition group [(125 +/- 11) pg/g] were significantly higher than that of the control group [(64 +/- 5) pg/g]; The levels of TNF-alpha in the homogenates of internal intercostal muscle of the malnutrition group [(119 +/- 11) pg/g] were significantly higher than that of the control group [(59 +/- 5) pg/g]. The contents of 3-methylhistidine in homogenates of diaphragmatic muscle [(7.1 +/- 0.6) nmol/g] and internal intercostal muscle [(7.4 +/- 0.6) nmol/g] of the malnutrition group were significantly higher than that of the control group [(4.0 +/- 0.5) nmol/g]. The contents of tyrosine in homogenates of diaphragmatic muscle [(639 +/- 24) nmol/g] and internal intercostal muscle [(660 +/- 25) nmol/g] of the malnutrition group were significantly higher than that of the control group [(579 +/- 26) nmol/g]. TNF-alpha in the respiratory muscle showed a strong positive correlation with proteolysis of respiratory muscle (r = 0.854, P < 0.01).


CONCLUSIONS
An increase of proteolysis of respiratory muscles was found in COPD rats, more significant in the malnutrition rats. TNF-alpha is one of the causes for the increase of proteolysis of respiratory muscles.
Sun
Sheng-hua
SH
Department of Respiratory Medicine, The Third Xiangya Hospital of Central South University, Changsha 410013, China.
Tang
Wen-xiang
WX
Liu
Chun
C
Lin
Hua
H
Yang
Hong-hui
HH
D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D009752:Nutritional Status; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012132:Respiratory Muscles / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D014409:Tumor Necrosis Factor-alpha