The Study On The Influence Of Indometacin To The Expression Of Bcl-2 And Bax Of The COPD Model Rat's Skeletal Muscle Apoptosis

Objective: To make the COPD rats models and use Indometacin to intervene in the COPD rats. Observe the expression of Bcl-2 and Bax and the rates of the diaphragm apoptosis and the extensor digitorum longus apoptosis. The study on the influence of indometacin to the expression of Bcl-2 and Bax of the COPD rat's skeletal muscle apoptosis.Methods: 100 healthy male adult Wistar rats were randomly divided into two groups: model group (n=80) and normal control group (n=20). The model group rat was performed with intratracheal instillation of PEE (20u/100g.Bw) on the 15th day of the modeling and exposed to cigarette smoke for 45 days, 30 minutes per day. The control group was not exposed to smoke but was intratracheally instilled of the same amount of Physiologic Saline on the 15th day. The model rats were continually exposed to cigarette smoke for another days. Malnutrition was defined when the weight of the rats in the model group was lower than 90% of the mean body weight of the control group. All model rats were redivided into 6 groups: the control group, the non-malnutrition COPD group, the malnutrition COPD group, Indometacin intervention group 1, Indometacin intervention group 2, Indometacin intervention group 3. Intragastriced administration physiologic saline to the control group, the non-malnutrition COPD group and the malnutrition COPD group and intragastriced administration Indometacin to Indometacin intervention group 1 (0.5mg/kg), Indometacin intervention group 2 (1.0mg/kg), Indometacin intervention group 3 (2.0mg/kg) respectively for 14 days, then kept raising for 14 days. Diaphragmatic muscle and long extensor muscle digits from rats were taken to make paraffin sections. The rates of muscle apoptosis were measured by TUNEL method, expression of related genes Bcl-2 and Bax by immunohistochemical method, and the intensity of the expression of Bcl-2 and Bax by Image J Imaging system to deal with the pictures. All the data was handled by SPSS 13.0 software through one-factor analysis of variance, t-test and related analysis.Results:1.The results showed that the rates of muscle apoptosis in both diaphragmatic muscle and extensor muscle digits of Indometacin intervention group 2 were lower than those of the the malnutrition COPD group, Indometacin intervention group 1 and Indometacin intervention group 3 (P<0.05) were significantly higher than those of the control group and the non-malnutrition group (P<0.05).Diaphragm cell apoptosis was higher than that of extensor digitorum cell compared in the same group, but with no statistical significance (P>0.05).2. The Bcl-2 protein expression of both diaphragmatic muscle and long extensor muscle digits was higher than those of the COPD malnutrition saline group, indometacin group 1 and indometacin group 3 (P<0.05). There were no significant differences between diaphragmatic muscle and long extensor muscle digits in the expression of Bcl-2 protein of the same group(P>0.05).3. The Bax protein expression of both diaphragmatic muscle and long extensor muscle digits was lower than those of the COPD malnutrition saline group, indometacin group 1 and indometacin group 3 (P<0.05). There were no significant differences between diaphragmatic muscle and long extensor muscle digits in the expression of Bax protein of the same group(P>0.05).Conclusion:1. Apoptosis maybe the important mechanism in skeletal muscle atrophy of COPD model rats. The genes Bcl-2 and Bax are the factors to adjust the muscle apoptosis of COPD model rats.2. The intervention of different dosage in indomethacin on the COPD malnutrition model rats, results suggest that 1.0mg/kg dose of indomethacin can improve the loses of cell in skeletal muscle of COPD malnutrition model rats.