基于MEK/ERK通路研究桂枝茯苓丸改善慢性阻塞性肺疾病小鼠气道重塑的作用与机制  

Study on the Effect and Mechanism of Guizhi Fuling Pill(桂枝茯苓丸)on Improving Airway Remodeling in COPD Mice Based on MEK/ERK Pathway

作　　者：邓秀娟[1] 杨亿然 张真 谭宇军[1] 刘雨[1] 黄乐 胡学军[1] DENG Xiujuan;YANG Yiran;ZHANG Zhen;TAN Yujun;LIU Yu;HUANG Le;HU Xuejun(Hunan Academy of Traditional Chinese Medicine Affiliated Hospital,Changsha Hunan,410006,China;Hunan University of Chinese Medicine,Changsha Hunan 410208,China)

机构地区：[1]湖南省中医药研究院附属医院,湖南长沙410006 [2]湖南中医药大学,湖南长沙410208

出　　处：《中医药导报》2024年第1期20-25,共6页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：湖南省中医药科研计划重点项目(2021206)。

摘　　要：目的:研究桂枝茯苓丸通过丝裂原活化细胞外信号调节蛋白激酶(MEK)/细胞外调节蛋白激酶(ERK)通路改善慢性阻塞性肺疾病(COPD)小鼠气道重塑的作用与机制。方法:采用烟熏的方法建立COPD小鼠模型,将32只造模成功小鼠随机分为模型组、桂枝茯苓丸组、PD98059组和桂枝茯苓丸+PD98059组,每组8只。另取8只未烟熏的小鼠为空白组。各组予相应药物灌胃14 d。采用小动物肺功能仪测定小鼠每分钟通气量(MV)、呼气峰值流速(PEF)和吸气峰值流速(PIF),HE染色评估肺组织炎症,Masson染色观察气道重塑改变,Western blotting检测COL1A1、COL3A1、MEK1、p-MEK1、ERK(1/2)和p-ERK(1/2)蛋白相对表达量。结果:模型组小鼠MV、PIF和PEF水平均低于空白组(P<0.05)。与空白组比较,模型组小鼠肺组织出现明显炎症和气道重塑,且肺组织COL1A1、COL3A1、p-MEK1、p-ERK(1/2)、p-MEK/MEK和p-ERK(1/2)/ERK(1/2)均高于空白组(P<0.05)。桂枝茯苓丸组、PD98059组和桂枝茯苓丸+PD98059组小鼠MV、PEF、PIF水平均高于模型组(P<0.05),肺组织COL1A1、COL3A1、p-MEK1、p-ERK(1/2)、p-MEK/MEK和p-ERK(1/2)/ERK(1/2)均低于模型组(P<0.05)。与模型组比较,桂枝茯苓丸组、PD98059组和桂枝茯苓丸+PD98059组小鼠的肺组织炎症和气道重塑改善。桂枝茯苓丸+PD98059组小鼠MV、PIF、PEF水平高于桂枝茯苓丸组和PD98059组(P<0.05)。桂枝茯苓丸组小鼠MV、PIF和PEF水平与PD98059组比较,差异无统计学意义(P>0.05)。桂枝茯苓丸组小鼠肺组织COL1A1和COL3A1蛋白相对表达量低于PD98059组(P<0.05),高于桂枝茯苓丸+PD98059组(P<0.05)。PD98059组小鼠肺组织COL1A1和COL3A1蛋白相对表达量高于桂枝茯苓丸+PD98059组(P<0.05)。桂枝茯苓丸组小鼠肺组织p-MEK1、p-ERK(1/2)、p-MEK1/MEK1和p-ERK(1/2)/ERK(1/2)低于PD98059组(P<0.05),高于桂枝茯苓丸+PD98059组(P<0.05)。PD98059组小鼠肺组织p-MEK1、p-ERK(1/2)、p-MEK1/MEK1和p-ERK(1/2)/ERK(1/2)高于桂枝茯苓丸+PD9805Objective To study on the effect and mechanism of Guizhi Fuling pill on improving airway remodeling in chronic obstructive pulmonary disease(COPD)mice through the MEK/ERK pathway.Methods:A COPD mouse model was established using smoking method.Totally 32 COPD model mice were randomly divided into model group,Guizhi Fuling pill group,PD98059 group and Guizhi Fuling pill+PD98059 group,with 8 mice in each group.Another 8 mice were selected as the blank group.Corresponding drugs were administered orally for 14 days.Small animal lung function analyzer was used to measure minute ventilation volume(MV),peak expiratory flow(PEF)and peak inspiratory flow(PIF)in mice.HE staining was used to evaluate lung tissue inflammation.Masson staining was used to observe airway remodeling changes,and Western blotting was used to detect the relative expression levels of COL1A1,COL3A1,MEK1,p-MEK1,ERK(1/2)and p-ERK(1/2)proteins.Results:The model group showed lower levels of MV,PIF and PEF than blank group(P<0.05).Compared with the blank group,there were significant inflammation and airway remodeling in lung tissue in model group.The model group showed higher levels of COL1A1,COL3A1,p-MEK1,p-ERK(1/2),p-MEK/MEK and p-ERK(1/2)/ERK(1/2)than blank group(P<0.05).Guizhi Fuling pill group,PD98059 group,and Guizhi Fuling pill+PD98059 group showed higher level of MV,PEF and PIF than model group(P<0.05),while lower levels of COL1A1,COL3A1,p-MEK1,p-ERK(1/2),p-MEK/MEK and p-ERK(1/2)/ERK(1/2)in lung tissue than model group(P<0.05).Compared with model group,lung tissue inflammation and airway remodeling were improved in Guizhi Fuling pill group,PD98059 group and Guizhi Fuling pill+PD98059 group.Guizhi Fuling pill+PD98059 group showed higher levels of MV,PIF and PEF than Guizhi Fuling pill group and PD98059 group(P<0.05),and there was no statistically significant difference in the levels of MV,PIF and PEF between Guizhi Fuling pill group and PD98059 group(P>0.05).Guizhi Fuling pill group showed lower relative expression levels of COL1A1 and COL3A1 protei

关 键 词：慢性阻塞性肺疾病 桂枝茯苓丸 气道重塑 MEK/ERK通路 PD98059 小鼠 

分 类 号：R285.5[医药卫生—中药学]