中国组织工程研究

中国组织工程研究 ›› 2019, Vol. 23 ›› Issue (25): 4050-4055.doi: 10.3969/j.issn.2095-4344.1792

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

人羊膜间充质干细胞移植对哮喘小鼠气道杯状细胞增生及黏蛋白5ac表达的影响

杨红霞，石清红，翁敏华，张建勇，赵建军，陈  玲
  

  1. 遵义医学院附属医院呼吸与危重症医学科呼吸二病区，贵州省遵义市  563003
  • 修回日期:2019-03-25 出版日期:2019-09-08 发布日期:2019-09-08
  • 通讯作者: 张建勇，博士，主任医师，遵义医学院附属医院呼吸与危重症医学科呼吸二病区，贵州省遵义市 563003
  • 作者简介:杨红霞，女，1985年生，2012年遵义医学院毕业，硕士，主治医师，主要从事支气管哮喘发病机制及治疗方面的研究。
  • 基金资助:

    贵州省科学技术基金项目(项目编号黔科合J字[2013]2329号)，项目负责人：杨红霞；贵州省科技计划课题(黔科合SY字[2015]3050)，项目负责人：赵建军

Effect of human amniotic mesenchymal stem cell transplantation on airway goblet cell proliferation and mucin 5ac expression in asthmatic mice

Yang Hongxia, Shi Qinghong, Weng Minhua, Zhang Jianyong, Zhao Jianjun, Chen Ling
  

  1. Second Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
  • Revised:2019-03-25 Online:2019-09-08 Published:2019-09-08
  • Contact: Zhang Jianyong, MD, Chief physician, Second Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
  • About author:Yang Hongxia, Master, Attending physician, Second Department of Pulmonary and Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
  • Supported by:

    the Scientific and Technological Fund Project of Guizhou Province, No. [2013]2329 (to YHX); the Scientific and Technological Plan Subject of Guizhou Province, No. [2015]3050 (to ZJJ)

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摘要：

文章快速阅读：

文题释义：
人羊膜间充质干细胞：是来源于产后胎盘羊膜组织的一种干细胞，取材简便，不受伦理限制，移植后存活时间长，不仅具有较强的细胞增殖能力和分化潜能，还具有低免疫原性、免疫调节功能等优点，可通过直接作用于免疫细胞或者分泌多种细胞因子，进一步介导免疫调节反应。
支气管哮喘：是由多种细胞和细胞组分参与的以气道慢性炎症和气道高反应性为特征的呼吸系统疾病，表现为广泛多变的可逆性气流受限，随着病程的延长而发生气道结构改变，即气道重塑。气道重塑过程中出现气道上皮杯状细胞增生、黏膜下腺体肥大等引起气道黏液高分泌。

 

摘要
背景：前期实验研究表明，人羊膜间充质干细胞移植可减轻哮喘小鼠气道炎症反应，但对哮喘小鼠气道黏液高分泌的影响尚不明确。
目的：探讨人羊膜间充质干细胞移植对哮喘小鼠气道杯状细胞增生及黏蛋白5ac表达的影响。
方法：28只BALB/C小鼠随机分为4组：假手术组(第1，13天给予生理盐水致敏，第19-23天给予生理盐水雾化激发)，模型组(给予卵清白蛋白致敏和雾化激发构建哮喘小鼠模型)，实验组(第18天给予哮喘模型小鼠尾静脉移植人羊膜间充质干细胞进行干预)，空白组(给予生理盐水致敏和雾化激发，第18天尾静脉移植人羊膜间充质干细胞进行干预)，每组7只小鼠。各组小鼠均于第24天处死，观察气道组织病理学变化、上皮杯状细胞增生情况，检测支气管肺泡灌洗液中白细胞介素5水平、肺组织中气道黏蛋白5ac蛋白和mRNA的表达水平。
结果与结论：①模型组支气管、血管周围及肺间质可见大量炎症细胞浸润，气道上皮杯状细胞增生明显，管壁不同程度增厚，部分管腔内见大量黏液分泌，管腔狭窄甚至闭塞；实验组气道炎症细胞浸润、杯状细胞增生情况较模型组减轻；②与假手术组和空白组比较，模型组气道上皮杯状细胞占总细胞的面积比例、杯状细胞数量、肺泡灌洗液中白细胞介素5水平、气道黏蛋白5ac蛋白和mRNA的表达量明显增高(P < 0.01)；与模型组比较，实验组上述指标明显降低(P < 0.01)；③结果表明，人羊膜间充质干细胞移植可以抑制哮喘小鼠气道炎症反应和上皮杯状细胞增生，下调气道黏蛋白5ac的表达，减轻气道黏液高分泌。


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程
ORCID: 0000-0002-8024-7796(张建勇)

关键词: 人羊膜间充质干细胞, 哮喘, 杯状细胞, 白细胞介素5, 黏蛋白5ac, 气道炎症反应, 气道黏液高分泌

Abstract:

BACKGROUND: Our preliminary studies indicated that human amniotic mesenchymal stem cells transplantation can reduce airway inflammatory responses in asthmatic mice, but the effect of human amniotic mesenchymal stem cells on airway mucus hypersecretion is unclear.
OBJECTIVE: To investigate the effect of human amniotic mesenchymal stem cells transplantation on airway goblet cell proliferation and mucin 5ac expression in asthmatic mice.
METHODS: Twenty-eight BALB/C mice were randomly divided into sham operation group (sensitized with normal saline at the 1st and 13th days, and motivated with nebulized normal saline at the 19th to 23th days), model group (sensitized with egg albumin and motivated with nebulized egg albumin to construct a mouse model of asthma), experimental group (transplanted with human amniotic mesenchymal stem cells via the tail vein of the mouse model of asthma at the 18th day), and blank group (sensitized with normal saline, motivated with nebulized normal saline, and transplanted with human amniotic mesenchymal stem cells via the tail vein at the 18th day). There were seven mice in each group. All the mice were sacrificed at the 24th day. We observed the pathological changes in the airway and the proliferation of epithelial goblet cells in each group. We detected the expression of interleukin-5 in the bronchoalveolar lavage fluid and the mRNA and protein levels of mucin 5ac in the lung tissue.
RESULTS AND CONCLUSION: (1) In the model group, there were a large amount of inflammatory cells infiltrated in the bronchus, perivascular and lung interstitial tissues; the goblet cells of the airway epithelium proliferated obviously, the tracheal wall was thickened to varying degrees, and there were a large amount of mucus secretion in some lumens with the lumen being narrow or even occluded. In the experimental group, airway inflammatory cell infiltration and goblet cell hyperplasia were alleviated. (2) Compared with the sham operation and blank groups, the model group showed increases in the proportion of airway epithelial goblet cells, number of goblet cells, interleukin-5 level in the bronchoalveolar lavage fluid, and expression of mucin 5ac protein and mRNA in the airway (P < 0.01). Compared with the model group, the above-mentioned indexes of the experimental group were significantly decreased (P < 0.01). All the findings indicate that transplantation of human amniotic mesenchymal stem cells can inhibit airway inflammatory response and epithelial goblet cell proliferation, downregulate mucin 5ac expression, and alleviate airway mucus hypersecretion.

Key words: human amniotic mesenchymal stem cells, asthma, goblet cells, interleukin-5, mucin 5ac, airway inflammatory response, airway mucus hypersecretion

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