复方佛耳草合剂对慢性阻塞性肺疾病模型大鼠气道重塑的干预作用及机制研究  

Effect of Compound Fo’ercao(佛耳草)Mixture on Airway Remodeling in Rats with Chronic Obstructive Pulmonary Disease and Its Mechanism

作　　者：廖健杉 折哲[1] 熊必丹[1] 刘佳玉 石克华[1] 李凤森 Liao Jianshan;Zhe Zhe;Xiong Bidan;Liu Jiayu;Shi Kehua;Li Fengsen(Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai 200071;Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200137;Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine,Urumqi 830000)

机构地区：[1]上海中医药大学附属市中医医院,上海200071 [2]上海中医药大学附属第七人民医院,上海200137 [3]新疆维吾尔自治区中医医院,乌鲁木齐830000

出　　处：《中药药理与临床》2022年第6期58-64,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家中管局专项基金(编号:JDZX2015231)。

摘　　要：目的:探讨复方佛耳草合剂对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)大鼠气道重塑的作用机制。方法:60只大鼠随机分为正常对照组、模型对照组、地塞米松0.5 mg/kg组、复方佛耳草合剂6.8、13.6、27.2 g/kg组。除正常对照组外,其余大鼠均采用香烟烟雾暴露联合气管注射脂多糖(LPS)建立COPD模型大鼠,复方佛耳草合剂和地塞米松于造模后第12 w灌胃给药,正常对照组和模型对照组灌胃给予等体积生理盐水,连续24 w。采用动物肺功能仪测定大鼠肺功能相关参数的变化;观察各组大鼠肺部病理变化;测定气管壁面积(WAt)、平滑肌面积(WAm)、管腔内周长(Pi)及平滑肌细胞核数(N);ELISA法测定血清及肺泡灌洗液中基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、转化生长因子β1(TGF-β1)及基质金属蛋白酶抑制剂-1(TIMP-1)含量变化;实时荧光定量PCR、Western blot法检测肺组织Mmp2、Mmp9、Tgfb1及Timp1 mRNA和蛋白表达情况。结果:与正常对照组比较,模型对照组大鼠存在肺通气功能障碍,肺组织和支气管病理改变明显,全身及肺组织MMP-2、MMP-9、TGF-β1以及TIMP-1含量升高,肺组织Mmp2、Mmp9、Tgfb1及Timp1 mRNA和蛋白表达显著上调(P<0.01);与模型对照组比较,复方佛耳草合剂13.6、27.2 g/kg组和地塞米松0.5 mg/kg组均能够改善肺通气功能障碍,减少支气管管壁平均厚度和平滑肌面积,降低血清与肺泡灌洗液MMP-2、MMP-9、TGF-β1及TIMP-1含量,下调肺组织Mmp2、Mmp9、Tgfb1及Timp1 mRNA和蛋白表达(P<0.05或P<0.01)。结论:复方佛耳草合剂能够改善COPD大鼠肺组织损伤和气道重塑,其机制可能与其能够下调MMP-2、MMP-9、TGF-β1以及TIMP-1蛋白和mRNA表达有关。Objective:To explore the mechanism of Compound Fo’ercao(佛耳草)Mixture in airway remodeling in rats with chronic obstructive pulmonary disease(COPD).Methods:Sixty rats were randomized into a normal group,a model group,a 0.5 mg/kg dexamethasone group,and 6.8 g/kg,13.6 g/kg and 27.2 g/kg Compound Fo’ercao Mixture groups.Except the normal group,rats in other groups were treated with smoke combined with lipopolysaccharide(LPS)injection to establish the model of COPD.Compound Fo’ercao Mixture and dexamethasone weregiven to rats in the corresponding groups by gavage on the 12th week,while the normal group and model group were given the same amount of normal saline.The treatment lasted for 24 weeks.The pulmonary function instrument was used to measure the changes in the parameters related to rat lung function.The pathological changes in rat lung tissues in each group were observed.The airway wall area(WAt),smooth muscle area(WAm),lumen circumference(Pi),and smooth muscle nucleus number(N)were measured.Moreover,the content of matrix metalloprotein-2(MMP-2),matrix metalloprotein-9(MMP-9),transforming growth factor-β1(TGF-β1),and tissue inhibitor of metalloproteinase-1(TIMP-1)in the serum and alveolar lavage fluid was detected by enzyme-linked immunosorbent assay(ELISA).Real-time quantitative polymerase chain reaction(RT-PCR)and Western blotting assay were conducted to measure the mRNA and protein expression levels of Mmp2、Mmp9、Tgfb1,and Timp1,respectively,in lung tissues.Results:Compared with the normal group,the model group had pulmonary ventilation dysfunction,and the pathological changes of lung tissue and bronchial were obvious.In the model group,the content of MMP-2,MMP-9,TGF-β1,and TIMP-1 in the body and lung tissues was increase(P<0.01),while the mRNA and protein expression levels of Mmp2、Mmp9、Tgfb1,and Timp1 in lung tissues were significantly up-regulated.Compared with the model group,13.6 g/kg and 27.2 g/kg Compound Fo’ercao Mixture groups and 0.5 mg/kg dexamethasone group improved pulmonary

关 键 词：复方佛耳草合剂 慢性阻塞性肺疾病 气道重塑 基质金属蛋白酶 基质金属蛋白酶抑制剂 转化生长因子 

分 类 号：R285.5[医药卫生—中药学]