二陈汤加味对慢性阻塞性肺疾病大鼠信号转导蛋白Smad3,4,6,7基因表达的影响  

Mechanism of Modified Erchentang on Expression of Smad 3,4,6,7 Genes in Lung Tissue of Rats with Chronic Obstructive Pulmonary Disease

作　　者：尚立芝[1] 季书 刘坦[1] 张静[1] 谢文英[1] 薛红莉 刘志勇[3] 赵献敏[1] 刘晓蕙[1] 孙春阳[1] 卢长青[3] 梁娟娟[1] 张淼[1] 王祎[1] 陈婷婷[1] SHANG Li-zhi JI Shu LIU Tan ZHANG Jing XIE Wen-ying XUE Hong-li LIU Zhi-yong ZHAO Xian-min LIU Xiao-hui SUN Chun-yang LU Chang-qing LIANG Juan-juan ZHANG Miao WANG Yi CHEN Ting-ting(Henan University of Chinese Medicine,Henan Medical College,The Second Affiliated Hospital of Henan University of Chinese Medicin)

机构地区：[1]河南中医药大学基础医学院,郑州450046 [2]河南医学高等专科学校,郑州451191 [3]河南中医药大学第二附属医院,郑州450008

出　　处：《中国实验方剂学杂志》2017年第10期139-146,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金面上项目(81573881);郑州市科技领军人才项目(121PLJRC535);河南省高等学校重点科研项目(15A360030);河南省科重点技攻关项目(152102310337);河南省中医药科学研究专项课题(2013ZY02070);河南中医学院大学生创新学习项目(CXXM[2016]0019;CXXM[2016]0041)

摘　　要：目的:观察二陈汤加味对慢性阻塞性肺疾病(COPD)大鼠肺组织中信号转导蛋白Smads的影响,探讨二陈汤加味对COPD作用的机制。方法:将50只SD大鼠随机分5组,每组10只动物,包括正常组、模型组、二陈汤加味低、中、高剂量(5,10,20 g·kg^(-1)·d^(-1))组。以烟熏加气管滴注脂多糖(LPS)的方法制备COPD大鼠模型。建模后,治疗组灌胃给药,正常组及模型组灌胃等量生理盐水。评价肺功能,实时荧光定量PCR(Real-time PCR)检测肺组织中Smad3,Smad4,Smad6和Smad7mRNA表达,免疫组织化学检测大鼠肺组织中Smad3,Smad4,Smad6,Smad7蛋白表达。结果:与正常组比较,模型组用力肺活量(forced vital capacity,FVC),第1秒末时间肺活量(FEV_1)和FEV_1/FVC均显著降低(P<0.01);模型组肺组织Smad3和Smad4 mRNA的表达量升高(P<0.05),Smad6和Smad7 mRNA表达均降低(P<0.05);Smad3和Smad4蛋白的表达显著增强(P<0.01),Smad6和Smad7蛋白的表达显著减弱(P<0.01)。与模型组比较,二陈汤加味中、高剂量组FVC,FEV_1和FEV_1/FVC均显著提高(P<0.01);Smad3和Smad4 mRNA的表达量均下降(P<0.05),Smad6和Smad7 mRNA的表达量升高(P<0.05);Smad3,Smad4蛋白的表达显著减弱(P<0.01),Smad6,Smad7蛋白的表达显著增强(P<0.01)。结论:二陈汤加味能有效抑制细支气管结构重塑作用。其机制可能是通过降低Smad3,提高Smad6和Smad7,协调Smad4基因表达,抑制细支气管及肺组织结构重塑。Objective： To study the effect of modified Erchentang on expression of Smad3,4,6,7 genes in the lung tissue of rats with chronic obstructive pulmonary disease（COPD）. Method： Fifty SD rats were randomly divided into normal group,model group,and low,middle and high-dose modified Erchentang groups（5,10,20 g·kg-1·d-1）. COPD model in rats was prepared by using cigarette smoke and dripping lipopolysaccharide（LPS） in trachea. After the modeling,normal and model groups were given normal saline solution through intragastric administration,while other groups were given corresponding herbal drugs intragastrically（5,10.20 g·kg-1·d-1） for 14 days. The pulmonary function was evaluated [forced vital capacity（FVC）,at the end of the first seconds forced expiratory volume（FEV1）]. The expressions of Smad3,Smad4,Smad6 and Smad7 mRNA were detected by quantitative real time PCR（Real-time PCR） method,and immunohistochemistry（IHC） method was used to detect the expression of Smad3,Smad4,Smad6,Smad7,TGF-β1and it＇s receptor（TGF-beta RI） protein in the lung tissue of all of the groups. Result： Compared with normal group,FVC,FEV1 and FEV1/FVC of the model group were decreased significantly（P〈0.01）; the expression of Smad3 and Smad4 mRNA and was increased（P〈0. 05）,the expression of Smad4 and Smad3 protein was increased significantly（P〈0.01）,the expression of Smad6 and Smad7 mRNA was decreased（P〈0. 05）,the expression of Smad7 and Smad6 protein was decreased significantly（P〈0.01） in model group. Compared with model group,FVC,FEV1 and FEV1/FVC index were increased significantly（P〈0.01）,the expression of Smad3 and Smad4 mRNA was decreased（P〈0. 05）,the expression of Smad3 and Smad4 protein was decreased significantly（P〈0.01）,but the expression of Smad6 and Smad7 mRNA was increased（P〈0. 05）,Smad6 and Smad7 protein was increased significantly（P〈0.01）,in modified Erchentang of 10 g·kg-1·d-1and 20 g·kg-1·d-1groups. Conclusion： Modified Er

关 键 词：慢性阻塞性肺疾病 二陈汤加味 信号转导 SMADS 

分 类 号：R285.5[医药卫生—中药学]