The Research Of Clenbuterol On Diaphragmatic Muscle Cell Apoptosis In The Models Of Copd Rats

Chronic obstructive pulmonary disease (COPD) due to its high rate of morbidity, disability and mortality costs many social resources. Now it has become an important public health problem worldwide. In China, COPD is also a dangerous chronic respiratory disease, which does much harm to the health people. Respiratory failure is a common and serious complication of COPD. In recent years, it was accepted that diaphragmatic fatigue took an important role on the physiological and pathological mechanisms of the respiratory failure.ObjectiveTo investigate the effect of clenbuterol on diaphragmatic muscle cell apoptosis and the expression of Fas (which led to the beginning of the apoptosis) in the models of chronic obstructive disease (COPD) rats.MethodsForty-five male Wistar rats were randomly dived into three equal groups, control group (group A), replication of COPD group (group B), clenbuterol group (group C). The each group was further divided into three subgroups of pre-replication, replication 2 w, 4 w subgroups (5 rats each). Groups B and C by inhaling smoke and injecting LPS into tracheas to replicate the models of COPD , group C was treated by clenbuterol after inhaling smoke every day .Apoptosis and Fas, caspase-3 expression of diaphragmatic muscle cell were examined by the streptavidin biotin-peroxidase complex immunohistochemistry techniques and terminal deoxynucleotidyl transferase-mediated d-UTP-biotin nick end labeling (TUNEL). The m-RNA of Fas was examined by RT-PCR. IGF-1 was examined by ELISA. Dunnett -t test was employed to compare the difference of each group. ResultsAfter 4 weeks the models of COPD were successfully replicated in the 4w-subgroups of B,C. Apoptosis rate and the expression of Fas,caspase-3, The m-RNA of Fas: there was not statistically significant difference between subgroups of group A, but 2 w, 4 w subgroups in groups of B and C were all statistically significant different compared with subgroups of A at the same time (all P<0.01), the differences were all statistically significant between 2 w, 4 w subgroups in groups of B and C (all P<0.05)The rate of group C ,except the pre-replication subgroups, the differences of other weeks were all statistically significant when compared with group B (all P<0.05). IGF-1: there was not statistically significant difference between subgroups of group A. but 2 w, 4 w subgroups of group B were all statistically significant lower compared with subgroup of pre-replication (P<0.05) .and there was statistically significant difference between 4 w subgroups in groups of B and C.ConclusionsSmoking and LPS took an important part in the process of diaphragmatic muscle cell apoptosis in the models of COPD rats. Clenbuterol can decreased diaphragmatic muscle cell apoptosis by inhibiting the reaction of oxidative-stress and down regulating the expression of Fas caspase-3,and add the expression of IGF-1, which contributed to the therapeutic effect on diaphragmatic fatigue of the models of COPD rats.