Abstract: Objective: To investigate the effects of montelukast (Mon) on the proliferation, apoptosis and secretion of inflammatory factors of the airway smooth muscle cells of the asthmatic rats, and to elucidate the molecular mechanism of airway remodeling and inflammatory response in the asthmatic rats. Methods: The acute asthma rat models were established by ovalbumin sensitization and stimulation.The primary cultured airway smooth muscle cells at the fifth generation were carried out for the experiment.The experiment was divided into control group (normal airway smooth muscle cells), model group (asthmatic model rat airway smooth muscle cells) and treatment group (asthmatic model rat airway smooth muscle cells +Mon intervention). The proliferation activities of the cells in various groups were detected by MTT method, the apoptotic rates of the cells in various groups were measured by flow cytometry, and the levels of interleukin-6(IL-6) and transforming growth factor-β1(TGF-β1) in cell supernatant in various groups were tested by ELISA method.The expression levels of proliferating cell nuclear antigen(PCNA), CyclinD1,B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein(Bax), Toll-like receptor-4(TLR4) and nuclear factor-κB (NF-κB) p65 proteins in the cells in various groups were examined by Western blotting method, and the expression levels of TLR4 and NF-κB p65 mRNA in the cells in various groups were detected by RT-PCR method. Results: Compared with control group, the proliferation activities of the cells in model group and treatment group were increased significantly(P<0.05), the apoptotic rates were decreased significantly(P<0.05), and the levels of IL-6 and TGF-β1 were obviously increased(P<0.05);the expression levels of PCNA, CyclinD1, Bcl-2, TLR4 and NF-κB p65 proteins and the expression levels of TLR4 and NF-κB mRNA were remarkably increased(P<0.05),but the expression levels of Bax protein was distinctly decreased(P<0.05).Compared with model group, the proliferation activity of the cells in treatment group was decreased (P<0.05), the apoptotic rate was increased (P<0.05), and the levels of IL-6 and TGF-β1 were clearly decreased(P<0.05);the expression levels of PCNA, CyclinD1, Bcl-2, TLR4 and NF-κB p65 proteins and the expression levels of TLR4 and NF-κB mRNA were remarkably decreased(P<0.05), but the expression levels of Bax protein was obviously increased (P<0.05). Conclusion: Mon can inhibit the proliferation of airway smooth muscle cells, promote the apoptosis and alleviate the airway inflammation in the asthmatic rats,and its mechanism may be related to inhibition of TLR4/NF-κB signaling pathway.

Key words: asthma, airway smooth muscle cells, montelukast, cell proliferation, inflammation