骨髓间充质干细胞移植对慢性哮喘小鼠气道炎症及气道重塑的影响

Effects of Bone Marrow-Derived Mesenchymal Stem Cells on Airway Inflammation and Airway Remodeling in Chronic Asthmatic Mice

目的探讨同种异体骨髓间充质干细胞(BMSC)移植对慢性哮喘小鼠气道炎症和气道重塑的影响。方法 40只雌性BALB/c小鼠随机分为正常对照组、BMSC对照组、哮喘模型组和BMSC治疗组。从雄性BALB/c小鼠分离BMSC。用卵白蛋白(OVA)制备慢性哮喘模型。观察BMSC移植对慢性哮喘小鼠气道炎症和气道重塑的影响,并采用流式细胞术检测BMSC对脾组织CD4+CD25+调节性T细胞比例的影响。结果哮喘模型组支气管上皮黏膜脱落,上皮黏膜有杯状细胞增生,部分管腔内有黏液栓塞,气道、血管旁有大量炎性浸润,以及气道平滑肌细胞增生和肥大。正常对照组及BMSC对照组无气道炎症及气道重塑的表现,而BMSC治疗组气道炎症及气道重塑明显减轻。与BMSC对照组及正常对照组比较,哮喘模型组CD4+CD25+调节性T细胞占淋巴细胞的比例显著降低(P<0.05);与哮喘模型组比较,BMSC治疗组CD4+CD25+调节性T细胞占淋巴细胞的比例明显提高(P<0.05);BMSC治疗组与正常对照组及BMSC对照组无显著差异。结论 BMSC移植能明显减轻慢性哮喘小鼠气道炎症及气道重塑程度,并能上调外周CD4+CD25+调节性T细胞的比例。

Objective To investigate the effect of allogeneic bone marrow-derived mesenchymal stem cells（BMSCs） transplantation on the airway inflammation and airway remodeling in chronic asthmatic mice.Methods Forty female BALB/c mice were equally randomized into four groups,ie.a normal control group,a BMSCs control group,an asthma model group,and a BMSCs transplantation group.BMSCs were generated from male donor mice,then the mice in the asthma model group and the BMSCs transplantation group were sensitized and challenged with OVA to establish chronic asthmatic mice model.Hematoxylin and eosin staining and Alcian blue-periodic acid-Schiff staining were used to analyze the effects on airway inflammation and airway remodeling after BMSC engraftment.The number of CD4＋CD25＋ regulatory T cells in spleen was detected by flow cytometry.Results In lungs of the asthma model group,there were intensive inflammatory cells infiltration around airway and blood vessels,goblet cell proliferation,epithelial desquamation,patchy airway occlusion by hyperviscous mucus,and hypertrophy of airway smooth muscle.Airway inflammation and airway remodeling were significantly relieved in the BMSCs transplantation group.There was no obvious inflammatory cells infiltration in the airway and airway remodeling both in the normal control group and the BMSCs control group.The number of CD4＋CD25＋ regulatory T cells in spleen significantly decreased in the asthma model group compared with the two control groups（P0.05）,and significantly increased in the BMSCs transplantation group compared with the asthma model group（P0.05）.There was no significant difference in the number of CD4＋CD25＋ regulatory T cells in spleen between the control groups and the BMSCs transplantation group.Conclusion BMSCs engraftment can up-regulate CD4＋CD25＋ regulatory T cells and relieve airway inflammation and airway remodeling in asthmatic mice.