Abstract: Objective To establish a chronic obstructive pulmonary disease (COPD) model by passive cigarette smoking and (or)
intratracheal instillation of lipopolysaccharide (LPS) in spontaneously hypertensive (SH) rats. Methods Fifteen male SH rats
were randomly divided into control group, cigarette smoking exposure (CS) group and CS+LPS (cigarette smoking exposure
plus intratracheal instillation of LPS) group. After 8 weeks’ treatment, the COPD model was validated by inspecting the
general condition and examining lung function and pulmonary pathological changes. The expressions of surfactant-associated
protein A (SP-A), NF-κB, histone, p-Iκ-Kα/β, Iκ-Kα/β, and IκB-α were determined with Western blotting, and the expression of
TNF-α and IL-6 mRNA were measured using qRT-PCR. Results The rats in both CS and CS+LPS groups were marantic with
intermittent cough and tachypnea. Lung function test showed increased RI and lowered peak expiratory flow in CS group,
which were more prominent in CS+LPS group (P<0.05). HE staining demonstrated typical chronic bronchitic inflammation
and emphysema in the lungs of the two model groups with significantly decreased mean alveolar number and significantly
increased mean lining intermiment and destrction index. The emphysema level was more serious in CS+LPS group than in CS
group. Western blotting showed markedly decreased expressions of SP-A and IκB-α in CS group and CS+LPS , especially the
latter group. The protein levels of NF-κB, Iκ-K phosphorylation and mRNA expressions of TNF-α and IL-6 increased
obviously in the two model groups. Conclusion COPD model can be established by passive smoking and (or) intratracheal
instillation of LPS in SH rats, and the model induced by combined exposures is optimal.