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
陈超辉 1汤昱 1董利利 1张磊 1赵二要 1郭燕军2
作者信息
- 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
- 折叠
摘要
目的 探讨硬尖神香草提取物通过转化生长因子-β1(transforming growth factor-β1,TGF-β1)/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-β1、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-β1 mRNA与α-SMA、TGF-β1、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-β1 mRNA、α-SMA、TGF-β1、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,硬尖神香草高剂量组和阳性药物组改善明显.结论 硬尖神香草提取物能有效抑制哮喘幼鼠气道重塑,可能通过调控TGF-β1/Smads通路调控相关mRNA和蛋白的表达,抑制EMT发挥作用.
Abstract
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-β1(TGF-β1)/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-β1,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-α and MMP-9 levels,the mRNA and protein levels of α-SMA,TGF-β1 and α-SMA,TGF-β1,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-α and MMP-9 levels,the mRNA and protein levels of E-cadherin increased,while the α-SMA,TGF-β1 mRNA and α-SMA,TGF-β1,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 improved to different degrees,and the improvement was obvious in the high-dose group and the positive drug group.Conclusion EHC can effectively inhibit airway remodeling in asthmatic young mice,possibly by regulating TGF-β1/Smads pathway to regulate related mRNA and protein expression and inhibit EMT.
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Key words
extract of Hyssopus cuspidatus Boriss(EHC)/asthma/epithelial-mesenchymal transformation/airway remodeling/transforming growth factor-β1/mothers against decapentaplegic homolog引用本文复制引用
基金项目
2018年河南省医学科技攻关计划项目(2018020599)
出版年
2024
NETL
NSTL
维普
万方数据