桔梗汤总皂苷对慢性阻塞性肺病大鼠IKK/NF-KB/MUC5AC通路的影响

Effect of totalsaponins of Radix Platycodonis Decoction on IKK/NF-KB/MUC5AC pathway in rats with chronic obstructive pulmonary disease

目的:考察桔梗汤总皂苷对慢性阻塞性肺病大鼠IKK/NF-KB/MUC5AC通路的影响,探讨桔梗汤总皂苷治疗COPD可能的分子机制。方法:建立COPD大鼠模型,将60只SD大鼠分为空白组、模型组、阳性对照组及不同剂量的桔梗汤总皂苷治疗组,经过3周治疗后,对比分析大鼠肺功能变化、肺灌洗液中IL-6、IL-8、IL-1β的含量、血清中S100A8、S100A9、LCN1、LCN2的含量、肺组织病理切片及IKK2、p-IKBα、NF-KB、MUC5AC蛋白表达量。结果:各个剂量的桔梗汤总皂苷均可显著改善COPD模型大鼠的肺功能受损,降低COPD大鼠肺灌洗液中IL-6、IL-8、IL-1β的含量,降低血清中S100A8、S100A9、LCN1、LCN2的含量,且均呈现良好的量效关系;另外高剂量的桔梗汤总皂苷在上述所有指标的检测中,与空白组大鼠无显著性差异;Western blot实验结果表明,桔梗汤总皂苷可显著降低COPD大鼠肺组织中IKK2、p-IKBα、NF-KB、MUC5AC蛋白表达,差异具有统计学意义。结论:桔梗汤总皂苷可显著改善COPD大鼠的肺功能,其机制是通过抑制高度活化的IKK/NF-KB/MUC5AC通路实现的。

OBJECTIVE To explore the effect of total saponins of Platycodon grandiflorum decoction(SPG)on IKK/NF-KB/MUC5 AC pathway in rats with chronic obstructive pulmonary disease(COPD)and elucidate the possible molecular therapeutic mechanism of SPG for COPD.METHODS After establishing a model of COPD,60 Sprague-Dawley rats were divided into the groups of blank,model,positive control and different therapeutic doses of SPG.After 3-week treatment,the following test parameters were compared:lung function changes,contents of interleukin-6(IL-6),interleukin-8(IL-8)and interleukin-1β(IL-1β)in lung lavage fluid,serum contents of S100 A8,S100 A9,LCN1,LCN2,pathological sections of lung tissue and protein expressions of IKK2,p-IKBα,NF-KB and MUC5 AC in lung tissue.RESULTS All doses of SPG could significantly improve lung function impairment,lower the contents of IL-6,IL-8 and IL-1βin lung lavage fluid,reduce the serum contents of S100 A8,S100 A9,LCN1,LCN2 and all demonstrated an excellent dose-effect relationship.Furthermore,high-dose SPG differed not significantly from those in blank group regarding all the above parameters.Western blot indicated that SPG could significantly lower the protein expressions of IKK2,p-IKBα,NF-KB and MUC5 AC in lung tissue.And the differences were statistically significant.CONCLUSION SPG can significantly improve lung function of COPD rats.The mechanism is achieved by a suppression of highly activated IKK/NF-KB/MUC5 AC pathway.