Topiramate Non-nepalese Ketone Bleomycin Model Of Pulmonary Fibrosis In Rats Caused By The Intervention And Its Possible Mechanism

ObjectiveTo investigate the effectiveness and the best dosage of pirfenidone(PF) for treating rat pulmonary fibrosis induced by bleomycin(BLM). To study the relationship between PF's antifibrotic effect and the expressions of transforming growth factor betal(TGF- β₁), matrix metalloprotease-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1). MethodMale Wistar rats, weighted 190-210g, were endotracheally instilled with BLM, or normal saline (NS). Rats were randomly separated into 12 groups: group N, endotracheal NS and gavage sodium carboxymethyl cellulose (CMC); group B, endotracheal BLM and gavage CMC; group P25, endotracheal BLM and gavage pirfenidone with 25mg/kg/day; group P5, endotracheal BLM and gavage pirfenidone with 50mg/kg/day; group P1, endotracheal BLM and gavage pirfenidone with 100mg/kg/day; group P2, endotracheal BLM and gavage pirfenidone with 200mg/kg/day; group P3, endotracheal BLM and gavage pirfenidone with 300mg/kg/day; group P4, endotracheal BLM and gavage pirfenidone with 400mg/kg/day; group P8, endotracheal BLM and gavage pirfenidone with 800mg/kg/day. Pirfenidone, desamethasone or 1% CMC was given daily by gavage from the day before instillation of BLM in those groups. Group P7 and P14, endotracheal BLM and gavage pirfenidone with 50mg/kg/day after 7 days or 14 days BLM instillation separately. Animals were sacrificed and lungs were harvested 28 days after BLM instillation. Lung collagen was stained by sirius red and measured by content of hydroxyproline. Expression of mRNA levels of TGF- β₁, MMP-13 and TIMP-1 was detected by reverse transcription-polymerses chain reaction(RT-PCR). Expression of proteins of TGF- β₁, MMP-13 and TIMP-1 was detected by immunohistochemistry and Western blotting. The TGF- β₁ levels in bronchoalveolar lavage fluid (BALF) were detected by ELISA.