复方佛耳草合剂抑制p38MAPK信号通路对COPD大鼠气道炎症的调控作用

Inhibition of p38MAPK Signal Pathway by Compound Verbena Mixture on Airway Inflammation in COPD Rats

目的 观察复方佛耳草合剂对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠气道炎症的调控作用。方法 60只大鼠分为正常组、模型组、丝裂原活化蛋白激酶p38(p38 mitogen-activated protein kinase,p38MAPK)抑制剂组、复方佛耳草合剂低、中、高剂量组。除正常组外,其余大鼠均采用香烟烟雾暴露联合气管注射脂多糖(lipopolysaccharide,LPS)建立COPD模型大鼠。模型建立成功后给予24周药物治疗,采用动物肺功能仪测定大鼠肺功能相关参数的变化,观察支气管-肺组织病理与超微结构改变,实时荧光定量聚合酶链式反应(Real time quantitative polymerase chain reaction, RT-qPCR)法测定肿瘤坏死因子(tumor necrosis factor,TNF)-α、白细胞介素(interleukin,IL)-8、p38MAPK及重组人激活转录因子-2(activating transcription factor-2,ATF-2)m RNA表达,Western blot法测定p38MAPK、ATF-2蛋白表达。结果 不同剂量复方佛耳草合剂均能改善大鼠通气功能障碍,修复受损肺组织,显著下调肺组织中TNF-α、IL-8、p38MAPK及ATF-2 m RNA水平(P<0.05,P<0.01)与p38MAPK、ATF-2蛋白表达(P<0.05,P<0.01),其中复方佛耳草合剂高剂量组疗效最佳。结论 复方佛耳草合剂具有改善COPD肺部炎症的作用,其具体机制可能与抑制p38MAPK通路相关。

Objective To observe the regulating effect of compound verbena Mixture on airway inflammation in chronic obstructive pulmonary disease(COPD)rats.Methods Sixty rats were divided into control group,model group,p38 mitogen-activated protein kinase(p38MAPK)inhibitor group,and low,medium,and high dose of the compound Verbena mixture group.In addition to the control group,the other rats were exposed to cigarette smoke combined with a tracheal injection of lipopolysaccharide(LPS)to establish COPD model rats.After the model was successfully established,drug treatment was given for 24 weeks.After drug administration,the rats had their lung function measured by the animal lung function instrument.The histomorphology changes and ultrastructure of the bronchial-pulmonary were observed.The mRNA expressions of tumor necrosis factor(TNF)-α,interleukin(IL)-8,p38MAPK,and activating transcription factor-2(ATF-2)were detected by Real time quantitative polymerase chain reaction(RT-qPCR),the protein expressions of p38MAPK,ATF-2 were detected by western blot.Results Different doses of compound Verbena mixture could improve lung ventilation dysfunction,repair damaged bronchial-pulmonary,significantly downregulated the expression mRNA of TNF-α,IL-8,p38MAPK and ATF-2(P<0.05,P<0.01),and decreased the protein expression of p38MAPK and ATF-2(P<0.05,P<0.01)in the lung tissues.Among them,the high dose of the compound Verbena mixture group had the best effect.Conclusion compound Verbena mixture could improve lung inflammation in COPD,and its mechanism may be related to the inhibition of the p38MAPK pathway.