关键词: 细颗粒物, 博来霉素, 肺纤维化, TLR2, TLR4, IL-6, TNF-α, TGF-β1

Abstract: Objective To investigate the effects of exposure to PM2.5 on bleomycin-induced pulmonary fibrosis in rats. Methods Rats were divided into four groups ：1) control group(group N); 2)PM2.5 group（group PM）; 3)BLM group（group B）; 4)PM2.5 plus BLM group （group PM+B）；Each group was divided into four groups. Rats were injected of normal saline (1.5mL/kg), PM2.5 suspended in saline（3.75mg/kg）, bleomycin (3.5mg/kg) and PM2.5 combined with BLM in saline into trachea respectively. The rats were sacrificed on day 3, 7, 14 and 21. The lung were stained with HE and Masson’s trichrome to estimate the degree of alveolitis and pulmonary fibrosis. Bronchoalveolar lavage fluid（BALF）was collected and cells in BALF were counted. The levels of IL-6 ,TNF-α and TGF- β1 in BALF were detected by the method of enzyme linked immunosorbent assay(ELISA). Western blot was performed to detect the protein levels of TLR2 and TLR4 in lung. The lung were made into tissue homogenate which were used for measuring the contents of HYP in pulmonary tissue. Results The body weight of rats in group B and group PM+B was significantly decreased compared with that in the group N. The rats in group B and group PM+B exhibited significant alveolar inflammatory and fibrosis changes compared with that of group N and group PM. The numbers of WBC in BALF and the concentration of IL-6 , TNF-α, TGF-β1 and hydroxyproline were significantly elevated in Group B and group PM+B compared with that in group N and group PM. The protein levels of TLR2 and TLR4 in the lungs in group B, group PM and group PM+B were significantly higher than that in group N. Conclusions Exposure to PM2.5 could impact the concentration of IL-6, TNF-α and TGF-β1 by increasing TLR2 and TLR4 expession, by which exaggerate BLM-induced inflammatory and fibrotic changes in the lung.

Key words: fine particulate matter, bleomycin, pulmonary fibrosis, TGF-β1, IL-6, TNF-α, TLR2, TLR4