Mechanism of sub-chronic crotonaldehyde exposure-induced pulmonary inflammation in male rats / 中国职业医学

ABSTRACT

OBJECTIVE: To observe the conditions of sub-chronic crotonaldehyde exposure-induced pulmonary inflammation,oxidative stress and apoptosis in male rats,and to explore the related mechanisms. METHODS: The specific pathogen free Wistar male rats were randomly divided into control group,low-,medium-and high-dose crotonaldehyde groups,with 10 rats in each group. Rats were treated with crotonaldehyde at the concentrations of 0. 0,2. 5,4. 5 and 8. 5 mg/kg body weight by intra-gastric administration,once per day for 120 consecutive days. After the end of treatment,rats were sacrificed,the lungs were weighed and histopathological examination was performed. The levels of malondialdehyde( MDA),superoxide dismutase( SOD) and glutathione peroxidase( GSH-Px) in the serum of rats were determined by colorimetry. The relative expression of reactive oxygen species in lung tissues was detected by fluorescence probe. The apoptosis rate was detected by Tunel staining. The relative expression of B-cell lymphoma( Bcl)-2,Bcl-2 associated X protein( Bax) and cysteine aspartic acid protease-3( Caspase-3) proteins in lung tissue was detected by western blotting.RESULTS: The body weight of the rats in the high-dose group began to decrease after 30 days of exposure( P < 0. 05),and the body weight in the low-and medium-dose groups began to decrease at 90 days exposure( P < 0. 05),when compared with that of the control group at the same time. The body weight of the high-dose group was lower than that of the low-and medium-dose groups began to decrease at 90 days exposure( P < 0. 05). After exposure,the lung tissue of the three doses groups showed different degrees of inflammatory change in a dose-effect relationship. The level of serum MDA in rats increased with the treatment of crotonaldehyde( P < 0. 01). The activities of serum SOD and GSH-Px decreased with the treatment of crotonaldehyde( P < 0. 01). The relative expression of ROS and apoptosis rate in rat lung tissue increased with the treatment of crotonaldehyde( P < 0. 01). The relative expression of Bcl-2 protein and the ratio of Bcl-2/Bax in the lung tissue of rats decreased with the treatment of crotonaldehyde( P < 0. 01). The relative protein expression of Bax and Caspase-3 increased with the treatment of crotonaldehyde( P < 0. 01). CONCLUSION: Crotonaldehyde sub-chronic exposure can cause apoptosis in lung tissue by altering the oxidative balance,leading to inflammatory pathological changes in the lung.