硬尖神香草提取物对哮喘幼鼠气道重塑的作用机制  

Mechanism of airway remodeling effect of the extract of Hyssopus cuspidatus Boriss in asthmatic young rats

作　　者：陈超辉 汤昱 董利利[1] 张磊[1] 赵二要 郭燕军 CHEN Chaohui;TANG Yu;DONG Lili;ZHANG Lei;ZHAO Eryao;GUO Yanjun(Department of Respiratory,Children’s Hospital Affiliated to Zhengzhou University/He’nan Children’s Hospital/Zhengzhou Children’s Hospital,Zhengzhou 450000,China;Department of General Internal Medicine,Children’s Hospital Affiliated to Zhengzhou University/He’nan Children’s Hospital/Zhengzhou Children’s Hospital,Zhengzhou 450000,China)

机构地区：[1]郑州大学附属儿童医院/河南省儿童医院/郑州儿童医院呼吸科,郑州450000 [2]郑州大学附属儿童医院/河南省儿童医院/郑州儿童医院普通内科,郑州450000

出　　处：《西北药学杂志》2024年第3期33-39,共7页Northwest Pharmaceutical Journal

基　　金：2018年河南省医学科技攻关计划项目(编号:2018020599)。

摘　　要：目的探讨硬尖神香草提取物通过转化生长因子-β_(1)(transforming growth factor-β_(1),TGF-β_(1))/母亲信号蛋白同源物(Mothers against decapentaplegic homologs,Smads)通路调控上皮-间质转化(epithelial-mesenchymal transformation,EMT)对哮喘幼鼠气道重塑的作用。方法将幼鼠随机分为模型组、硬尖神香草(提取物)低剂量组(25 mg·kg^(-1))和硬尖神香草高剂量组(50 mg·kg^(-1))及阳性药物组(二羟丙茶碱,20 mg·kg^(-1)),各20只,另设对照组。比较支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)各类炎症细胞数及细胞因子白细胞介素-4(interleukin-4,IL-4)、基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的水平,HE染色观察肺组织病变,比较肺组织气道壁、平滑肌厚度,对比E钙黏蛋白(E-cadherin)、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、TGF-β_(1)、母亲信号蛋白同源物2(Mothers against decapentaplegic homolog 2,Smad2)以及母亲信号蛋白同源物3(Smad3)mRNA与蛋白的表达水平。结果与对照组比较,模型组嗜酸性粒细胞(eosinophil,EOS)、中性粒细胞(neutrophil,NEU)、淋巴细胞(lymphocyte,LYM)细胞数、支气管气道壁、平滑肌厚度、IL-4、TNF-α、MMP-9水平以及α-SMA、TGF-β_(1) mRNA与α-SMA、TGF-β_(1)、p-Smad2和p-Smad3蛋白水平均升高,E-cadherin mRNA与蛋白水平降低(P<0.05);与模型组比较,硬尖神香草低剂量组和高剂量组、阳性药物组的EOS、NEU、LYM细胞数、支气管气道壁、平滑肌厚度、IL-4、TNF-α、MMP-9以及E-cadherin mRNA和蛋白水平均升高,α-SMA、TGF-β_(1) mRNA、α-SMA、TGF-β_(1)、p-Smad2与p-Smad3蛋白水平均降低(P<0.05);且各指标水平变化规律是阳性药物组最明显,硬尖神香草高剂量组次之,硬尖神香草低剂量组最弱(P<0.05);HE结果显示,硬尖神香草低剂量和高剂量组、阳性药物组肺组织支气管气道损伤较模型组出现不同程度改善,硬�Objective To investigate the effect of the extract of Hyssopus cuspidatus Boriss(EHC)on airway remodeling in asthmatic infant rats by regulating epithelial-mesenchymal transition(EMT)through transforming growth factor-β_(1)(TGF-β_(1))/Mothers against decapentaplegic homologs(Smads)pathway.Methods The young rats were randomly divided into model group,low-dose EHC group(10 mg·kg^(-1)),high-dose EHC group(40 mg·kg^(-1))and positive drug group(dihydroxypropylline,20 mg·kg^(-1)),and control group,with 20 rats in each group.The number of inflammatory cells and the levels of cytokines interleukin-4(IL-4),matrix metalloproteinase 9(MMP-9)and tumor necrosis factor-α(TNF-α)in bronchoalveolar lavage fluid(BALF)were compared.The lung tissue lesions were observed by HE staining,and the thickness of airway wall and smooth muscle of lung tissue,the mRNA and protein expression of E-cadherin,α-smooth muscle actin(α-SMA),TGF-β_(1),Mothers against decapentaplegic homolog 2(Smad2),Mothers against decapentaplegic homolog 3(Smad3)were compared.Results Compared with the control group,the number of eosinophil(EOS),neutrophil(NEU)and lymphocyte(LYM)cells,bronchial airway wall and smooth muscle thickness,IL-4,TNF-αand MMP-9 levels,the mRNA and protein levels ofα-SMA,TGF-β_(1) andα-SMA,TGF-β_(1),p-Smad2 and p-Smad3 were increased,while the mRNA and protein levels of E-cadherin were decreased in model group(P<0.05).Compared with the model group,the number of EOS,NEU and LYM cells,bronchial airway wall and smooth muscle thickness,IL-4,TNF-αand MMP-9 levels,the mRNA and protein levels of E-cadherin increased,while theα-SMA,TGF-β_(1) mRNA andα-SMA,TGF-β_(1),p-Smad2,p-Smad3 protein levels decreased in the low and high dose EHC groups and positive drug group(P<0.05);Moreover,the changes in the levels of various indices were the most obvious in the positive drug group,followed by the high dose EHC groups,and the lowest was the low dose EHC groups(P<0.05).HE results showed that,compared with the model group,the injury was impro

关 键 词：硬尖神香草提取物 哮喘 上皮-间质转化 气道重塑 转化生长因子-β1 母亲信号蛋白同源物 

分 类 号：R965[医药卫生—药理学]