[Therapeutic effects of pulmonary surfactant on smoking-induced lung injury in rats, an experimental study].
OBJECTIVE
To investigate the therapeutic effects of pulmonary surfactant (PS) on smoking-induced lung injury in rats.


METHODS
Thirty male Wistar rats were randomly divided into four groups: normal control group (n = 8, killed by the end of the 7th week), 3-week smoking group (n = 8, in haling mainstream smoke of cigarette for 3 weeks and killed by the end of the 3rd week), 7-week smoking group (n = 8, in haling mainstream smoke of cigarette for 7 weeks and killed by the end of the 7th week), and PS treatment group (n = 6, inhaling mainstream smoke of cigarette for 7 weeks and given PS 25 mg/kg via trachea per week for 4 weeks since the end of the 3rd week of smoking, totally 5 times, and then killed by the end of the 7th week). The histological changes of respiratory bronchioles were observed by light microscopy and transmission electron microscopy. The airway resistance in expiratory phase was tested by pulmonary function test apparatus. The expression of Clara cell 16KD protein (CC16) mRNA and SP-C mRNA in lung tissue was determined by RT-PCR and the expression of CC16 protein in bronchiole epithelial cells was determined by immunohistochemistry.


RESULTS
The proportion of Clara cell to the respiratory bronchiole epithelial cells was 62% in the normal controls, 40% in the 3-week smoking group, 33% in the 7-week smoking group, and 56% in the PS treatment group (significantly lower in comparison with that in the 7-week group, P < 0.05). Degeneration of Clara cells, hyperplasis of type II pneumocytes and increase of area of smooth muscle in bronchioles were observed in the three smoking groups, however, such changes were the most distinct in the 7-week smoking group and the less distinct in the PS treatment group (P < 0.05). In comparison with those in the normal control group, the expression of CC16 mRNA, SP-C mRNA and CC16 protein were lower in the three smoking groups. However, the expressions of CC16 mRNA and the expression of SP-C mRNA in the PS treatment group were significantly higher than those in the 7-week smoking group (11.8 +/- 5.1 vs 3.0 +/- 0.9, and 8.5 +/- 3.4 vs 2.5 +/- 0.9, both P < 0.05). The mean area of smooth muscle in bronchioles with the diameter less than 200 micro m was significantly larger than that in the control group, however, the mean area in the PS treatment group was significantly less than that in the 7-week smoking group (P < 0.05). The airway resistance in the control group (1.62 +/- 0.08 cmH(2)O. L(-1). s(-1)) was lower than those in the 3 smoking groups, however, the airway resistance in the PS treatment group was significantly lower than that in the 7-week group (1.70 +/- 0.07 cmH(2)O. L(-1). s(-1) vs 2.98 +/- 0.65 cmH(2)O. L(-1). s(-1), P < 0.05).


CONCLUSIONS
PS is effective in alleviating smoking-induced lung injury in rats. One of the mechanisms might be attenuation of the damage in Clara cells and type II pneumocytes due to cigarette smoking.
Chi
Chunhua
C
Department of Pulmonary Medicine, The First Hospital, Peking University, Beijing 100034, China.
He
Bing
B
Zhang
Hong
H
Tang
Xiuying
X
D000818:Animals; D008168:Lung / Q000473:pathology / Q000648:ultrastructure; D008171:Lung Diseases / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D011506:Proteins / Q000235:genetics; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics; D011663:Pulmonary Surfactants / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012907:Smoking / Q000009:adverse effects*; D014598:Uteroglobin
D011506:Proteins; D037721:Pulmonary Surfactant-Associated Protein C; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D014598:Uteroglobin