慢性阻塞性肺疾病模型大鼠核因子κB及肿瘤坏死因子α、白细胞介素8的表达水平及其意义

Expression levels and significance of nuclear factor kappaB, tumor necrosis factor α and interleukin 8 in rat model of chronic obstructive pulmonary disease

目的探讨慢性阻塞性肺疾病(COPD)大鼠核因子κB (NF-κB)及肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-8的表达水平及其意义。方法将48只SD大鼠随机分为正常对照组(A组)、COPD组(B组)、COPD并低氧组(C组)、空白对照组(A1组)、COPD干预组(B1组)、COPD并低氧干预组(C1组),每组8只。A组及A1组均正常饲养,其余4组采用烟熏联合气管滴注脂多糖制作COPD模型;同时,C组及C1组在COPD建模最后2周给予氮气降低氧浓度以建立COPD并低氧模型。在实验第15天,B1组、C1组开始腹腔注射NF-κB抑制剂吡咯烷二硫代氨基甲酸盐,A1组注射等体积生理盐水。实验6周后,镜下观察各组大鼠肺组织病理学情况,检测各组大鼠肺组织中NF-κB p65蛋白表达水平,以及肺泡灌洗液(BALF)和血清IL-8、TNF-α表达水平。结果 B组、C组肺动脉中膜面积、肺动脉中膜厚度、肌性动脉率高于A组及对应干预组,且C组气管中膜面积、气管中膜厚度高于A组及C1组(均P<0.05)。B组、C组肺组织NF-κB p65蛋白、BALF及血清IL-8和TNF-α水平均高于A组及对应干预组(均P<0.05)。结论 COPD大鼠的NF-κB及TNF-α、IL-8等炎症因子的表达均上调;NF-κB可能通过调节TNF-α、IL-8等早期炎症介质的表达,从而参与COPD大鼠肺血管重塑、肺动脉高压的形成过程。

Objective To investigate the expression levels and significance of nuclear factor kappaB(NF-κB), tumor necrosis factor α(TNF-α) and interleukin(IL)-8 in rats with chronic obstructive pulmonary disease(COPD). Methods Forty-eight SD rats were randomly divided into normal control group(group A), COPD group(group B), COPD and hypoxia group(group C), blank control group(group A1), COPD intervention group(group B1), and COPD and hypoxia intervention group(group C1), with 8 rats in each group. Groups A and A1 received normal feeding, and the remaining four groups used fumigation combined with intratracheal instillation of lipopolysaccharide to develop COPD model;in addition, groups C and C1 were given nitrogen to reduce oxygen concentration in the last two weeks of COPD modeling so as to establish a model of COPD plus hypoxia. On the 15 th day of the experiment, groups B1 and C1 began to accept intraperitoneal injection of NK-κB inhibitor pyrrolidinedithiocarbamate ammonium, group A1 was injected with isometric normal saline. After six weeks of experiment, the pathological changes of lung tissue of rats in each group were observed under microscope, the expression level of NF-κB p65 protein in lung tissue, as well as the expression levels of IL-8 and TNF-α in bronchoalveolar lavage fluid(BALF) and serum were detected in each group. Results Groups B and C had greater pulmonary artery media area and media thickness, and a higher rate of muscular artery than group A and corresponding intervention groups, moreover, group C exhibited greater tracheal media area and media thickness than groups A and C1( all P<0.05). Groups B and C yielded a higher level of NF-κB p65 protein in lung tissue as well as higher levels of IL-8 and TNF-α in BALF and serum in comparison with group A and corresponding intervention groups(all P<0.05). Conclusion The expression of inflammatory factors such as NF-κB, TNF-α and IL-8 is up-regulated in COPD rats;NF-κB may involve in pulmonary vascular remodeling and pulmonary hypertension development by regulating the expression of early inflammation mediators TNF-α and IL-8.