RESUMO
OBJECTIVE: To explore dysfunction mechanism of rat alveolar type II (AT-II) injured by bleomycin (BLM). METHODS: SD rats were injected with a single intratracheal dose of bleomycin or control saline. On day 7, 14, and 28 following intratracheal bleomycin or saline instillation, animals were killed under overdose of 1.5% sodium pentobarbital (0.25 ml/100 g, i.p.) and bronchoalveolar lavage fluid (BALF) from the lung was tested for the activity of pulmonary surfactant (PS) by the Whihelmy Film Balance. Several concentrations of bleomycin stimulated the culture of rat AT-II cells, and surfactant protein (SP) A, B, and aquaporin-1 (AQP) mRNA were analyzed by fluorescent quantitative polymerase chain reaction (FQ-PCR). RESULTS: The activity of PS and hypoxemia significantly decreased on day 7 and improved on day 14 and completely recovered to normal status on day 28. SP-A, B, and AQP-1 mRNA expression in BLM-stimulated group were significantly lower than those in the control group (P<0.001). CONCLUSION: BLM-injured AT-II cells decrease the levels of SP-A, B, and AQP-1 mRNA and cause PS dysfunction, resulting in hypoxemia and pneumonedema.
Assuntos
Aquaporina 1/biossíntese , Bleomicina/toxicidade , Alvéolos Pulmonares/citologia , Proteína A Associada a Surfactante Pulmonar/biossíntese , Proteína B Associada a Surfactante Pulmonar/biossíntese , Animais , Aquaporina 1/genética , Bleomicina/administração & dosagem , Células Cultivadas , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Hipóxia/induzido quimicamente , Hipóxia/metabolismo , Hipóxia/patologia , Masculino , Alvéolos Pulmonares/efeitos dos fármacos , Proteína A Associada a Surfactante Pulmonar/genética , Proteína B Associada a Surfactante Pulmonar/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
OBJECTIVE: To explore the possible effects and mechanism of Fufang Biejiafang on a single intratracheal instillation (IT) of bleomycin-induced lung fibrosis model. METHOD: SD rats were treated with a single IT dose of bleomycin or control saline. Chinese medicine group were poured into the stomach after the first day of operation with high dosage, middle dosage and low dosage. On days 7, 14 and 28 following IT bleomycin or saline, 4 mL blood were taken from the abdominal aorta for arterial blood gas analysis. The left lung was fixed for routine light microscopic examination. Bronchoalveolar lavage fluid (BALF) from the right lung was tested the activity of pulmonary surfactant (PS) by the Whihelmy Film Balance, then the right lung was frozen immediately in liquid nitrogen for determination of hydroxyproline concentration. RESULT: Model rats had obviously changes of body weight and hypoxemia and dysfunction of PS on days 7 and improved on days 14. Compared with three dose groups, the middle dose group some degreely improved and PS function. It ameliorate fibrosis because of inhibition of inflammation. CONCLUSION: (1) PS dysfunction resulted in hypoxemia after bleomycin injured alveolar type II (AT II). Fufang biejiafang-middle dose-group ameliorate hypoxemia by remission AT-II injury. (2) Fufang biejiafang may inhibit exudation inflammation and ameliorate fibrosis.