红霉素对吸烟大鼠气道上皮细胞NF-κB和ICAM-1表达的影响

The Effect of Erythromycin on Nuclear Factor Kappa B and Intercellular Adhesion Molecule-1 in Airway Epithelium of Smoking Rat

目的通过观察红霉素对吸烟大鼠气道上皮细胞核因子-κB(NF-kappaB,NF-κB)和细胞间黏附分子-1(in-tercellular adhesion molecule-1,ICAM-1)表达的影响,探讨红霉素在慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)治疗中的抗炎作用。方法Wistar大鼠30只,体重150±10g,随机抽取20只被动吸烟4周后,10只继续吸烟8周作为吸烟组、10只吸烟前给予红霉素灌胃作红霉素组,另10只作对照组。测定气道阻力和肺顺应性,采用免疫组织化学方法测定各组大鼠气道上皮细胞NF-κB和ICAM-1的表达水平。结果(1)与对照组(2.74±0.21;6.03±0.47)比较,吸烟组(5.67±0.32;4.39±0.40)和红霉素组(4.14±0.18;4.99±0.63)气道阻力均升高,肺顺应性均降低,P均<0.01。与吸烟组比较,红霉素组气道阻力降低,P<0.01,肺顺应性升高,P<0.05。(2)与对照组(11.84±0.75;12.05±0.57)比较,吸烟组(21.04±0.54;19.09±0.39)和红霉素组(13.75±0.45;13.91±0.32)气道上皮细胞NF-κB和ICAM-1的表达明显增高,P均<0.05。与吸烟组比较,红霉素组气道上皮细胞NF-κB和ICAM-1的表达降低,P<0.05。(3)气道上皮细胞NF-κB与ICAM-1的表达呈明显正相关(R=0.991;P<0.01)。结论吸烟可以使大鼠气道阻力增高,肺顺应性降低,引起气道上皮细胞NF-κB和ICAM-1表达升高,红霉素可以改善吸烟引起的肺功能减退,并可能通过影响NF-κB和ICAM-1的表达而在慢性阻塞性肺疾病治疗中发挥一定的抗炎作用。

Objective To explore the anti - inflammatory therapeutic role of erythromycin in chronic obstructive pulmonary disease （COPD） by investigating the effect of erythromycin on the level of nuclear factor kappa B （ NF - κB） and intercellular adhesion molecule - 1 （ ICAM - 1 ） in airway epithelium of smoking rats. Methods Wistar rats （ n = 30） with weighed （ 150 ±10） g each,20 were randomly sampled to be exposed to cigarettes smoking for four weeks then 10 of them were exposed wntinuously to cigaretts smoking for eight weeks as smoking, group, other loof them were intragastrically perfused by erythromycih before smoking as evythromycin group, the rest of total 30 rats as control group Then assessed expiratory airway resistance and lung compliance and observed the expression level of NF -κB and ICAM - 1 in airway epithelium by using immunohistochemical method. Results （ 1 ） The expiratory airway resistance was increased and the lung compliance was degraded significantly in smoking group（5.67 ±0. 32,4. 39 ± 0. 40） （P 〈 0. 01 ）and erythromycin group （4.14 ±0. 18;4.99 ±0. 63） （P 〈0. 01 ） in contrast with control group（2.74 ±0. 21,6.03 ±0. 47） ,in erythromycin group the airway resistance（P 〈 0.01 ） was lower and the lung compliance （P 〈 0.05 ） was higher than that in smoking group. （2） The level of NF -κB and ICAM - 1 in smoking group（21.04 ± 0.54 、19.09 ±0. 39） and erythromycin group （ 13.75 ±0. 45,13.91 ±0.32 ） were obviously increased in airway epithelium as compareed with control group（ 11.84 ±0.75,12. 05 ±0. 57） （P 〈0.05） ,In erythromycin group,the level of NF -κB and ICAM - 1 were decreased as compared with smoking group （ P 〈 0. 05 ）. （ 3 ） airway epithelial cells NF - κB and theexpressiou of ICAM - 1 were positive correlated （ R =0. 991 ; P 〈 0. 01 ）. Conclusion Smoking can increase the airway resistance, degrade the lung compliance and increase the level of NF - κB and ICAM - 1 in airway epithelium, erythromycin can degrade the airway resistance,increase the lung compliance and restrain the expression of NF - κB and ICAM - 1 in airway epithelial cell,suggesting that erythromycin may play a certainly role in the anti - inflammatory therapeutics in COPD.