补肺益肾方对COPD大鼠气道黏液高分泌及肺组织Notch3,HES1的影响  

Effect of Bufei Yishen Prescription on Airway Mucus Hypersecretion and Notch3 and HES1 Expression in Lung Tissues of Rats with Chronic Obstructive Pulmonary Disease

作　　者：梅晓峰[1] 吴婉柳 肖振亚 任周新[1] 余海滨[1,2] MEI Xiao-feng;WU Wan-liu;XIAO Zhen-ya;REN Zhou-xin;YU Hai-bin(Henan University of Chinese Medicine,Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan&Education Ministry of P.R.,Henan Key Laboratory of Chinese Medicine for Respiratory Disease,Zhengzhou 450046,China;The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450046,China)

机构地区：[1]河南中医药大学呼吸疾病中医药防治省部共建协同创新中心,河南省中医药防治呼吸病重点实验室,郑州450046 [2]河南中医药大学第一附属医院,郑州450000

出　　处：《中国实验方剂学杂志》2022年第3期68-75,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81473650);河南省中医管理局河南省中医药科学研究专项(2017ZY2043)。

摘　　要：目的:观察补肺益肾方对慢性阻塞性肺疾病(COPD)大鼠气道黏液高分泌及Notch信号通路相关蛋白Notch3,HES家族发状分裂相关增强子1(HES1)的影响,探讨其作用机制。方法:将48只SD大鼠随机分为空白组、模型组、补肺益肾方组和氨茶碱组,每组12只。第1~12周,采用香烟烟雾暴露联合反复细菌感染方法制备COPD稳定期大鼠模型;第13~20周,空白组和模型组给予生理盐水灌胃,治疗组给予相应药物灌胃(补肺益肾方组3.7 g·kg^(-1)·d-1,氨茶碱组54 mg·kg^(-1)·d-1)。第20周灌胃结束后取材,观察肺组织病理,检测大鼠肺功能,肺泡灌洗液肿瘤坏死因子-α(TNF-α),白细胞介素-6(IL-6),黏蛋白5AC(MUC5AC)和肺组织Notch3,HES1,MUC5AC mRNA与蛋白表达水平。结果:与空白组比较,模型组大鼠肺功能显著降低(P<0.05,P<0.01),平均肺泡数显著降低(P<0.01),肺泡平均截距显著升高(P<0.01),肺泡灌洗液TNF-α,IL-6和MUC5AC显著升高(P<0.01),肺组织Notch3,HES1和MUC5AC基因与蛋白表达显著升高(P<0.05,P<0.01);与模型组比较,补肺益肾方组和APL组肺功能和肺病理损伤显著改善(P<0.05,P<0.01),肺泡灌洗液TNF-α,IL-6和MUC5AC显著降低(P<0.01),肺组织Notch3,HES1和MUC5AC基因与蛋白表达显著降低(P<0.05,P<0.01)。结论:补肺益肾方抑制COPD大鼠气道黏液高分泌,其机制与调控Notch3,HES1蛋白有关。Objective:To observe the effects of Bufei Yishen prescription on airway mucus hypersecretion and Notch signaling pathway related protein Notch3 and enhancer of split homologue 1(HES1)in rats with chronic obstructive pulmonary disease(COPD)and to explore its action mechanism.Method:Forty-eight SD rats were randomly divided into the control group,model group,Bufei Yishen prescription group,and aminophylline(APL)group,with 12 rats in each group.The stable COPD rat model was established via cigarette smoking exposure combined with Klebsiella bacterial infection for 12 weeks,and the corresponding drugs(3.7 g·kg^(-1)·d-1 Bufei Yishen prescription and 54 mg·kg^(-1)·d-1APL)were administered by gavage during the next eight weeks.After the last administration at week 20,the lung tissue was sampled for observing the pathological changes and the rat lung function was detected.The tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and mucoprotein 5AC(MUC5AC)in bronchial alveolar lavage fluid and the mRNA and protein expression levels of Notch3,HES1,and MUC5AC in lung tissues were assayed.Result:Compared with the control group,the model group exhibited significantly weakened pulmonary function(P<0.05,P<0.01),reduced average number of alveoli(P<0.01),elevated mean linear intercept(P<0.01),and up-regulated TNF-α,IL-6,and MUC5AC in bronchial alveolar lavage fluid and Notch3,HES1,and MUC5AC mRNA and protein expression in lung tissue(P<0.05,P<0.01).Compared with the model group,Bufei Yishen prescription and APL remarkably enhanced pulmonary function,alleviated its pathological injury(P<0.05,P<0.01),and down-regulated TNF-α,IL-6,and MUC5AC in bronchial alveolar lavage fluid and the mRNA and protein expression levels of Notch3,HES1,and MUC5AC in lung tissues(P<0.05,P<0.01).Conclusion:The mechanism of Bufei Yishen prescription in inhibiting airway mucus hypersecretion of COPD rats was related to its regulation of Notch3 and HES1.

关 键 词：补肺益肾方 慢性阻塞性肺疾病(COPD) NOTCH3 HES家族发状分裂相关增强子1(HES1) 气道黏液高分泌 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学]