抗支糖浆联合糖皮质激素对咳嗽变异性哮喘模型大鼠NF-κB信号通路的影响

Effects of Anti-bronchial Syrup Combined with Glucocorticoid on NF-κB Signaling Pathway in Model Rats with Cough Variant Asthma

目的:研究抗支糖浆联合糖皮质激素对咳嗽变异性哮喘模型大鼠NF-κB信号通路的影响。方法:选择SD大鼠50只,随机分为对照组、模型组、抗支糖浆组、糖皮质激素组和联合用药组,每组10只。第1天除对照组外其余四组采用卵蛋白(OVA)加氢氧化铝腹腔注射,7d一次,共注射3次,构建大鼠哮喘模型。第21天各组雾化吸入卵蛋白,对照组用生理盐水,3次/周,30min/次。各给药组于雾化激发前30min药物预处理,对照组用等量生理盐水处理。激发3周后,采用HE染色观察肺组织的病理学改变,测量支气管壁厚度、平滑肌厚度。westernblot检测大鼠肺部组织IκB、NF-κB、MMP-9和VEGF蛋白表达量。结果:HE染色发现联合用药组能够明显改气道壁上皮组织坏死、脱落,和大量炎性细胞浸润状况;支气管壁和平滑肌增厚分析发现:与对照组相比,其余四组的支气管壁和平滑肌显著增厚(P<0.05);与模型组相比,药物治疗组的组织增厚程度明显降低,联合用药组显著低于单独用药组(P<0.05);与对照组相比,其余四组的IκB蛋白表达明显减少,NF-κB、MMP-9和VEGF表达量显著增加(P<0.05);与模型组相比:单独用药组与联合用药组中IκB蛋白表达显著增加,NF-κB、MMP-9和VEGF表达明显降低(P<0.05),其中联合用药组的蛋白表达变化程度显著高于单独用药组(P<0.05)。结论:抗支糖浆联合糖皮质激素地塞米松能够降低IκB蛋白水解,减少NF-κB蛋白释放,下调MMP-9和VEGF蛋白表达抑制咳嗽变异性哮喘模型大鼠气道重塑。

Objective:To study the effects of anti-bronchial syrup combined with glucocorticoid on NF-κB signaling pathway in model rats with cough variant asthma.Methods:50 SD rats were selected and randomly divided into control group,model group,anti-bronchial syrup group,glucocorticoid group and combined group,with 10 rats in each group.On the 1st day of the experiment,the other four groups except control group were injected intraperitoneally with ovalbumin(OVA)and aluminum hydroxide,and they were treated for three times with once/7days for rat asthma model construction.On the 21st day of the experiment,they were given ovalbumin inhalation for atomization stimulation,and control group was stimulated with normal saline for 3 times/week with 30 min/time.Each drug-administered group was pretreated with drugs at 30 min before atomization stimulation,and control group was treated with the same amount of normal saline.3 weeks after stimulation,HE staining was used to observe the pathological changes of the lung tissue,and the thickness of airway wall and the thickness of smooth muscle were measured.Western blot was used to detect the expression levels of IκB,NF-κB,MMP-9 and VEGF proteins in rat lung tissue.Results:HE staining showed that combined group could significantly improve the airway wall epithelial tissue necrosis and shedding,and a large number of inflammatory cell infiltration.The analysis of airway wall and smooth muscle thickening showed that the airway wall and smooth muscle thickening in the other four groups were significantly thickened compared with control group(P<0.05).Compared with model group,the degree of tissue thickening in drug-treated groups was significantly decreased,and the degree in combined group was significantly lower than that in single drug groups(P<0.05).Compared with control group,the expression level of IκB protein was significantly decreased in the other four groups,and the expression levels of NF-KB,MMP-9 and VEGF were significantly increased(P<0.05).Compared with model group,the expression level of IKB protein in single drug groups and combined group was significantly increased,and the expression levels of NF-KB,MMP-9 and VEGF were significantly decreased(P<0.05),and the changes of protein expression in combined group were significantly higher than those in single drug groups(P<0.05).Conclusion:Kangzhi syrup combined with dexamethasone can reduce the hydrolysis of IκB protein,decrease the release of NF-κB protein,down regulate the expression of MMP-9 and VEGF,and inhibit the airway remodeling of cough variant asthma rats.