桂枝茯苓丸对慢性阻塞性肺疾病小鼠气道重塑的影响  

Effects of Guizhi Fuling Pills on airway remodeling in mouse models of COPD

作　　者：张真 杨亿然 刘雨[2] 谭宇军[2] 吴哲[2] 谭光波[2] 胡学军[2] 邓秀娟[2] ZHANG Zhen;YANG Yi-ran;LIU Yu;TAN Yu-jun;WU Zhe;TAN Guang-bo;HU Xue-jun;DENG Xiu-juan(Hunan University of Chinese Medicine,Changsha 410208,China;The Hospital Affiliated to Hunan Academy of Traditional Chinese Medicine,Changsha 410006,China)

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

出　　处：《中成药》2023年第11期3592-3598,共7页Chinese Traditional Patent Medicine

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对慢性阻塞性肺疾病(COPD)小鼠气道重塑的影响。方法40只C57BL/6小鼠随机分为空白组、模型组、桂枝茯苓丸组、EVP4593(NF-κB抑制剂)组和桂枝茯苓丸+EVP4593组,每组8只。采用烟熏的方法建立COPD小鼠模型,成模后予以相应药物灌胃14 d。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染色半定量评估肺组织炎症和气道管壁厚度,Masson染色观察气道纤维化改变,ELISA法检测肺组织IL-6、IL-8和TNF-α水平,Western blot法检测肺组织E-cadherin、α-SMA、Snail、IκBα、NF-κB、p-IκBα和p-NF-κB蛋白表达。结果与模型组比较,各给药组小鼠肺组织炎症评分、气道管壁厚度、气道蓝染胶原纤维区降低(P<0.05),肺功能指标MV、PEF和PIF值升高(P<0.05),肺组织IL-6、IL-8和TNF-α水平降低(P<0.05),肺组织E-cadherin蛋白表达升高(P<0.05),α-SMA、Snail、p-IκBα和p-NF-κB蛋白表达降低(P<0.05),p-IκBα/IκBα和p-NF-κB/NF-κB比值降低(P<0.05),其中以桂枝茯苓丸+EVP4593组作用最为显著(P<0.05)。结论桂枝茯苓丸可通过抑制NF-κB/Snail信号通路所介导的上皮间质转化(EMT)改善COPD气道重塑。AIM To study the effects of Guizhi Fuling Pills on airway remodeling in mouse models of chronic obstructive pulmonary disease(COPD).METHODS Forty C57BL/6 mice were randomly divided into the blank group,the model group,Guizhi Fuling Pills group,EVP4593(NF-κB inhibitor)group and Guizhi Fuling Pills+EVP4593 group,with 8 mice in each group.The successful mouse models of COPD established by cigarette smoke exposure were given 14 days corresponding drugs by gavage.The mice had their minute ventilation(MV),peak expiratory flow rate(PEF)and peak inspiratory flow rate(PIF)measured by small animal lung function instrument;their lung inflammation and airway wall thickness semi-quantitatively evaluated by HE staining;their airway fibrosis observed by Masson staining;their levels of IL-6,IL-8 and TNF-αin lung tissue detected by ELISA;and their protein expressions of E-cadherin,α-SMA,Snail,IκBα,NF-κB,p-IκBαand p-NF-κB in lung tissue detected by Western blot.RESULTS Compared with the model group,each treatment group shared decreased lung inflammation score,airway wall thickness,airway blue stained collagenous fiber area(P<0.05);increased levels of lung function indices MV,PEF and PIF(P<0.05);decreased lung levels of IL-6,IL-8 and TNF-α(P<0.05);increased pulmonary E-cadherin protein expression(P<0.05);decreased protein expressions ofα-SMA,Snail,p-IκBαand p-NF-κB(P<0.05);and decreased ratios of p-IκBα/IκBαand p-NF-κB/NF-κB(P<0.05),especially in Guizhi Fuling Pills+EVP4593 group(P<0.05).CONCLUSION Guizhi Fuling Pills can improve airway remodeling in mouse COPD models by inhibiting epithelial-mesenchymal transition(EMT)mediated by NF-κB/Snail signaling pathway.

关 键 词：桂枝茯苓丸 慢性阻塞性肺疾病 EVP4593 气道重塑 上皮间质转化 NF-κB/Snail信号通路 

分 类 号：R285[医药卫生—中药学]