补肺益肾方对COPD大鼠气道胶原沉积及肺组织Notch4、Hes1蛋白表达的影响  

Effect of Bufei Yishen Formula on airway remodeling and Notch 4 and Hes1 protein expression in lung tissue of COPD rats

作　　者：熊周璇 吴婉柳 肖振亚 任周新[1,2,3] 沈俊岭[4] 余海滨[1,2,4] XIONG Zhou-xuan;WU Wan-liu;XIAO Zhen-ya;REN Zhou-xin;SHEN Jun-ling;YU Hai-bin(Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan&Education Ministry of P.R.,Henan University of Chinese Medicine,Zhengzhou,Henan 450046,China;HenanKey Laboratory of Chinese Medicine far Respiratory Disease,Henan University of Chinese Medicine,Zhengzhou,Henan 450046,China;Academy of Chinese Medicine Science,Henan University of Chinese Medicine,Zhengzhou,Henan 450046,China;First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou,Henan,450000,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,河南郑州450046 [2]河南中医药大学河南省中医药防治呼吸病重点实验室,河南郑州450046 [3]河南中医药大学中医药科学院,河南郑州450046 [4]河南中医药大学第一附属医院,河南郑州450000

出　　处：《时珍国医国药》2022年第1期21-25,共5页Lishizhen Medicine and Materia Medica Research

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

摘　　要：目的观察补肺益肾方对慢性阻塞性肺疾病(Chronic obstructive pulmonary disease,COPD)模型大鼠气道胶原沉积的影响,并从NOTCH信号通路方面初步探讨其机制。方法将SPF级SD大鼠根据随机数字表法分为四个组:空白组、模型组、补肺益肾方组(BY)、氨茶碱组(APL)。除空白组外,其它组连续12周采用香烟烟雾暴露联合细菌感染的方法制备COPD稳定期动物模型,然后给予对应药物[补肺益肾方:生药11.61g/(kg·d);氨茶碱:54mg/(kg·d)]灌胃治疗。检测大鼠潮气量(Tidal Volume,TV)、呼气峰流速(Peak Expiratory Flow,PEF)、用力肺活量(Forced Vital Capacity,FVC)、0.3s用力呼气量(Forced Expiratory Volume in 0.3s,FEV 0.3);苏木素—伊红(HE)染色法观察大鼠肺组织病理改变;免疫组织化学法(IHC)检测大鼠肺组织Ⅰ型胶原、Ⅲ型胶原(collagen,Col)及Notch4、Hes1蛋白表达水平。结果与空白组相比,模型组大鼠肺功能FEV0.3、FVC显著降低(P<0.05),肺功能TV、PEF显著降低(P<0.01),肺泡腔可见大量炎性细胞浸润,肺泡结构破坏,气道壁增厚明显,Col Ⅰ、Col Ⅲ、Notch4、Hes1表达显著提高(P<0.01)。与模型组相比,BY和APL组大鼠肺功能TV、PEF、FVC显著提高(P<0.01),BY和APL组肺组织病变明显改善,Col Ⅰ、Col Ⅲ表达显著降低(P<0.05),Notch4、Hes1表达显著降低(P<0.01),APL组FEV0.3显著提高(P<0.05)。与APL组相比,BY组肺功能、Col Ⅰ、Col Ⅲ表达未见明显差异,Notch4、Hes1表达显著降低(P<0.05)。结论补肺益肾方可能通过调控NOTCH信号通路来改善COPD大鼠气道胶原沉积。Objective To observe the effect of Bufei Yishen Formula on airway collagen deposition and NOTCH signaling pathway in Chronic obstructive pulmonary disease(COPD)rats.Methods SD Rats of SPF level were divided into four groups according to random number table:Control group,Model group,Bufei Yishen formula group(BY)and aminophylline group(APL).The stable COPD animal model was induced by cigarette smoke exposure combined with bacterial infection.The model was established for 12 weeks,and then the corresponding drugs were given by gavage for 8 weeks.The tidal volume(TV)and peak expiratory flow(PEF)were measured by WBP,the forced vital capacity(FVC)and 0.3 s forced expiratory volume(FEV0.3)of rats were observed by PFT system;hematoxylin eosin(HE)staining was used to observe the pathological changes of lung tissue;immunohistochemistry(IHC)was used to detect the protein expression levels of collagen I,collagen III(Col),Notch4 and Hes1 in lung tissue.Results compared with the Control group,the lung function FEV0.3 and FVC of the Model group were significantly decreased(P<0.05),and the pulmonary function TV and PEF were significantly decreased(P<0.01),a large number of inflammatory cells infiltration,destruction of alveolar structure and thickening of airway wall were observed in the alveolar cavity,the expression of colⅠ,colⅢ,Notch4 and Hes1 increased significantly(P<0.01).Compared with the Model group,the lung function TV,PEF and FVC of the BY and APL groups were significantly increased(P<0.01).The lung lesions of the BY and APL groups were significantly improved,and the expressions of colⅠand colⅢwere significantly decreased(P<0.05),the expression of Notch4 and Hes1 was significantly decreased(P<0.01),FEV0.3 of the APL group was significantly increased(P<0.05).Compared with APL group,there was no significant difference in lung function and the expression of colⅠand colⅢin BY group,but the expression of Notch4 and Hes1 was significantly decreased(P<0.05).Conclusion Bufei Yishen Formula may improve the collagen

关 键 词：慢性阻塞性肺疾病 补肺益肾方 NOTCH信号通路 胶原 气道重塑 

分 类 号：R285.5[医药卫生—中药学]