[Establishment of a chronic obstructive pulmonary disease model by passive cigarette smoking and intratracheal LPS instillation in spontaneously hypertensive rats].
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 intermittent and destruction 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.


CONCLUSIONS
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.
Department of Respiratory Disease, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.E-mail: ych4231@gmail.com.
Changhui
C
Yu
Yan
Y
Chen
Ting
T
Li
Wei
W
Li
Shaoxi
S
Cai
Ying
Y
Meng
D000818:Animals; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology*; D051381:Rats; D011918:Rats, Inbred SHR; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D008070:Lipopolysaccharides; D014028:Tobacco Smoke Pollution