肺表面活性物质对吸烟致肺损伤大鼠的治疗作用

Therapeutic effects of pulmonary surfactant on smoking-induced lung injury in rats, an experimental study

目的 探讨肺表面活性物质 (PS)对吸烟致肺损伤大鼠的治疗作用。方法 使Wistar大鼠吸入烟草雾制作肺损伤大鼠模型。将大鼠随机分为正常对照组 (8只 )、吸烟 3周组 (8只 )、吸烟 7周组 (8只 )及PS治疗组 (6只 )。观察形态学、肺功能、肺组织CC16、SP CmRNA表达及细支气管上皮细胞CC16蛋白的表达。结果 吸烟 7周组细支气管Clara细胞比例降低 ,Ⅱ型肺泡上皮细胞增生 ,小气道壁平滑肌面积增加 (P <0 0 5 ) ,CC16、SP CmRNA及CC16蛋白表达均降低 (P <0 0 5 )。与吸烟 7周组比较 ,PS治疗组大鼠Clara细胞比例增加 (P <0 0 5 ) ,Ⅱ型肺泡上皮细胞增生程度减轻 ,小气道平滑肌面积降低 (P <0 0 5 ) ,气道阻力下降 (P <0 0 5 ) ,CC16、SP CmRNA及CC16蛋白表达均增高 (P <0 0 5 )。结论 PS治疗吸烟致肺损伤大鼠是有效的 ;

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, inhaling mainstream smoke of cigarette for 3 weeks and killed by the end of the 3rd week), 7-week smoking group (n=8, inhaling 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 loewer 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 μm 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 aiway resistance in the control group (1.62±0.08 cmH 2O·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 2O·L -1·s -1 vs 2.98±0.65 cmH 2O·L -1·s -1, P<0.05). Conclusion 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.