首页  期刊介绍 征稿简则 编委会 期刊征订 广告服务 留言板 联系我们 English

中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (6): 611-615.doi: 10.12047/j.cjap.6001.2020.128

• 研究论文 • 上一篇    下一篇

多配体蛋白多糖-1在慢性阻塞性肺疾病大鼠肺上皮间质转化中的作用及机制*

金艳1, 刘文明2   

  1. 1.南京医科大学附属常州第二人民医院急诊内科, 江苏 常州 213000;
    2.南京医科大学附属常州第二人民医院重症监护室, 江苏 常州 213000
  • 收稿日期:2020-02-26 修回日期:2020-11-25 出版日期:2020-11-28 发布日期:2021-03-15
  • 通讯作者: Tel: 13915056315; E-mail: lwmicu@163.com
  • 基金资助:
    *河南省新乡医学院第一附属医院青年培育基金项目(QN-2017-B027)

The role of syndecan-1 in the transformation of pulmonary epithelial stroma in rats with chronic obstructive pulmonary disease and its mechanism

JIN Yan1, LIU Wen-ming2   

  1. 1. Department of Emergency Medicine, Changzhou 213000, China;
    2. ICU, Second People's Hospital of Changzhou Affiliated to Nanjing Medical University, Changzhou 213000, China
  • Received:2020-02-26 Revised:2020-11-25 Online:2020-11-28 Published:2021-03-15

摘要: 目的:探讨多配体蛋白多糖-1(syndecan-1)在慢性阻塞性肺疾病(COPD)大鼠肺上皮间质转化(EMT)中的作用及机制。方法:选择清洁级SD雄性大鼠30只,随机分为假手术组(暴露气管后注射生理盐水,n=10),COPD组(注射1 mg/ml脂多糖后进行烟熏,造模完成后转染100 μl空载病毒,n=10),syndecan-1过表达组(注射1 mg/ml脂多糖后进行烟熏。造模完成后转染100 μl携带大鼠syndecan-1基因的重组腺病毒载体Ad-CMV-GFP-SDC1,n=10),每天1次,连续处理2周。处理结束后检测各组大鼠肺功能并取肺组织;采用HE染色法观察肺组织损伤情况;采用免疫组化检测各组大鼠肺组织syndecan-1、波形蛋白(vimentin)、E-钙黏蛋白(E-cadherin)的蛋白表达;采用Western blot检测转化生长因子-β1(TGF-β1)、Smad2/3和p-Smad2/3蛋白表达水平;采用qRT-PCR法检测各组大鼠肺组织中vimentin、E-cadherin、TGF-β1和Smad2/3 mRNA表达水平。结果:与假手术组相比,COPD组大鼠气道黏膜脱落,管腔狭窄,气道壁较多炎性细胞浸润,肺气肿严重,每分钟呼气量(VE)、最大呼气流量(PEF)和0.3s用力呼气容积(FEV0.3)和肺组织E-cadherin mRNA表达水平均显著降低(P<0.05),而vimentin、TGF-β1、Smad2/3 mRNA表达水平及TGF-β1、Smad2/3和p-Smad2/3的蛋白表达水平均显著升高(P<0.05)。与COPD组相比,syndecan-1过表达组气道黏膜脱落及气道壁炎性细胞浸润数减少,管腔狭窄、肺气肿情况均有所改善,VE、PEF、FEV0.3和肺组织E-cadherin mRNA表达水平显著升高(P<0.05),而vimentin、TGF-β1、Smad2/3 mRNA表达水平及TGF-β1、Smad2/3和p-Smad2/3的蛋白表达水平均显著降低(P<0.05)。结论:COPD大鼠体内TGF-β/Smad信号通路活化且存在肺EMT;过表达syndecan-1可抑制TGF-β/Smad信号通路,减轻EMT,改善COPD大鼠肺组织损伤。

关键词: 多配体蛋白多糖-1, 慢性阻塞性肺疾病, 大鼠, 上皮间质转化

Abstract: Objective: To explore the role and mechanism of polysaccharide-1 (syndecan-1) in the transformation of lung epithelial stroma (EMT) in rats with chronic obstructive pulmonary disease (COPD). Methods: Thirty male SD rats of clean grade were randomly divided into sham operation group (normal saline injection after tracheal exposure, n=10), COPD group (fumigation after injection of 1 mg/ml lipopolysaccharide, transfection of 100 μl empty virus, n=10) and syndecan-1 overexpression group (fumigation after injection of 1 mg/ml lipopolysaccharide, and transfection of 100 μl carrying rat syndecan-1 gene Ad-CMV-GFP-SDC1, n=10), once a day for two weeks. After the treatment, the lung function was detected and lung tissues were collected. HE staining was used to observe lung injury. The expression levels of syndecan-1, vimentin and E-cadherin in lung tissue of rats in each group were detected by immunohistochemistry. Western blot was used to detect the expressions of TGF-β1, Smad2/3 and p-Smad2/3. The mRNA levels of vimentin, E-cadherin, TGF-β1 and Smad2/3 were detected by qRT-PCR. Results: Compared with the sham operation group, the airway mucosa of COPD group was exfoliated, the lumen was narrow, the airway wall was more inflammatory cell infiltration, emphysema was serious, expiratory volume (VE), peak expiratory flow (PEF), Forced expiratory volume in 0.3 s (FEV0.3) and the expression of E-cadherin mRNA were significantly decreased (P<0.05). While the expression of vimentin, TGF-β1 and Smad2/3 mRNA were increased, and the expression levels of TGF-β1, Smad2/3 and p-Smad2/3 protein were significantly increased (P<0.05). Compared with COPD group, the number of airway mucosa exfoliation and inflammatory cell infiltration in airway wall were decreased, lumen stenosis and emphysema were improved, the levels of VE, PEF, FEV0.3 and the expression of E-cadherin mRNA were significantly increased (P<0.05). And the expressions of vimentin, TGF-β1 and Smad2/3 mRNA were decreased, and expression levels of TGF-β1, Smad2/3 and p-Smad2/3 protein were significantly decreased (P<0.05). Conclusion: In COPD rats, TGF-β/Smad signal pathway activation induced the production of EMT; overexpression of syndecan-1 could inhibit the EMT mediated by TGF-β/Smad signal pathway, and improve the lung tissue injury of COPD rats.

Key words: syndecan-1, COPD, rat, EMT

中图分类号: 

版权所有 © 2015 《中国应用生理学杂志》编辑部
京ICP备16058274号-1
地址:天津市和平区大理道1号,邮编:300050  电话:022-84655184  E-mail:tjzgyish@163.com
本系统由北京玛格泰克科技发展有限公司设计开发 技术支持:support@magtech.com.cn