间充质干细胞对哮喘模型小鼠的免疫调节作用:局部与全身应用效果不同  

Intravenous versus intratracheal administration of mesenchymal stem cells in a mouse model of asthma

作　　者：姚银[1,2] 郭洁波 邓学泉 孙悦奇[1,2] 付清玲[1,2] 

机构地区：[1]中山大学附属第一医院耳鼻咽喉科医院,广东省广州市510080 [2]中山大学耳鼻咽喉科研究所,广东省广州市510080

出　　处：《中国组织工程研究》2015年第28期4478-4484,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81170896);广东省科技计划(2012B031800045)~~

摘　　要：背景:研究显示间充质干细胞移植可以减轻呼吸道变应性炎症的相关症状,然而尚无不同移植途径下间充质干细胞对哮喘疗效的比较。目的:观察间充质干细胞不同应用方式对小鼠哮喘模型的免疫调节作用的区别。方法:Balb/c小鼠72只进行3次独立的实验,每次24只。将24只小鼠按随机数字表法等分为对照组、模型组、全身应用组和局部应用组。模型组、全身应用组和局部应用组小鼠分别在第1,7,14天以进行3次卵清蛋白腹腔注射致敏,第22-26天卵清白蛋白溶液持续雾化吸入30 min,连续激发5 d。全身应用组和局部应用组小鼠于雾化前1 d分别经尾静脉注入200μL间充质干细胞混悬液(5×109 L-1)和气管注入50μL间充质干细胞混悬液(2×1010 L-1)。结果与结论:与正常组相比,模型组小鼠气道炎症反应显著增强,间充质干细胞的全身应用可以下调气道高反应,降低肺泡灌洗液中炎症细胞数量,减轻肺组织中的炎症浸润,抑制血清中卵清白蛋白特异性IgE的分泌,降低肺泡灌洗液中Th2型细胞因子的水平;而间充质干细胞的局部应用对上诉症状无改善。间充质干细胞的全身应用可有效减轻哮喘小鼠的气道炎症反应,而其局部应用无改善作用。提示间充质干细胞不适合采用经气管内注射的应用方式,可能需经全身血循环发挥免疫调节作用。BACKGROUND：Several studies have demonstrated that mesenchymal stem cel s exhibit strong immunomodulation on al ergic asthma. However, there are no reports to compare therapeutic effects under different administration ways. OBJECTIVE：To examine the immunomodulatory effects of MSCs via different administration routes on asthmatic mice. METHODS：Seventy-two Balb/c mice experienced three independent tests, and 24 mice were selected for each test. Twenty-four mice were randomly divided into four groups （n=6）：control group, model group, intravenous treatment group and intratracheal treatment group. The mouse model of asthma was induced via intraperitoneal injection of ovalbumin at 1, 7, 14 days and 30-minute aerosol inhalation of ovalbumin at 22-26 days. In the latter two groups, mesenchymal stem cel s were injected intravenously （200μL, 5x109/L） or intratracheal y （50μL,2x109/L） into the mice at 1 day before aerosol inhalation. RESULTS AND CONCLUSION：Compared with the control group, the airway inflammatory response was significantly increased in the model group. Intravenous administration of mesenchymal stem cel s significantly al eviated the symptoms of al ergic airway inflammation, including the airway hyperreactivity, the inflammatory cel counting in the bronchoalveolar lavage fluid, inflammatory cel infiltration in the lung tissue. Meanwhile, the levels of Th2 type cytokines in the bronchoalveolar lavage fluid and IgE in serum also decreased after intravenous administration of mesenchymal stem cel s. However, the intratracheal application of mesenchymal stem cel s did not exhibit the similar effects. Intravenous, not intratracheal, application of mesenchymal stem cel s can exert immunomodulatory effects through the blood circulation.

关 键 词：干细胞 骨髓干细胞 哮喘 间充质干细胞 卵清蛋白 全身应用 局部应用 炎症 气道炎症反应 国家自然科学基金 

分 类 号：R394.2[医药卫生—医学遗传学]