骨髓间充质干细胞逆转支气管哮喘小鼠气道重塑及其机制的初步研究

目的：探讨骨髓间充质干细胞逆转支气管哮喘(简称哮喘)小鼠气道炎症及对气道重塑的影响。方法采用40只雄性的 BALB/c 小鼠,随机分组为骨髓间充质干细胞对照组、骨髓间充质干细胞治疗组、哮喘模型组、正常对照组。从4周龄雄性小鼠中分离出骨髓间充质干细胞。应用卵白蛋白制备慢性哮喘小鼠模型,采用流式细胞计数法检测小鼠外周血中 CD4+、CD25+调节性 T 细胞的情况,并观察骨髓间充质干细胞抑制之后气道的重塑及气道炎症的情况。结果病理检查可见哮喘模型支气管上皮黏膜有杯状细胞增生,上皮黏膜脱落,部分管腔有大量的炎性细胞浸润,气道平滑肌细胞肥大增生。正常对照组与骨髓间充质干细胞对照组无气道重塑及炎症表现,而骨髓间充质干细胞治疗组有气道炎症并且气道重塑现象明显。哮喘模型组的 CD4+、CD25+调节性 T 细胞比例较骨髓间充质干细胞对照组及正常对照组明显降低(F =12.346、14.528,P 值均<0.05)；骨髓间充质干细胞治疗组 CD4+、CD25+调节性 T 细胞比例较哮喘组明显上升(F =9.438,P <0.05)；而骨髓间充质干细胞治疗组、骨髓间充质干细胞对照组、正常对照组之间差异无统计学意义。结论骨髓间充质干细胞可逆转哮喘小鼠的气道炎症和气道重塑的程度,是通过上调 CD4+、CD25+调节性 T 细胞的比例发挥作用的。

Preliminary study on reversing airway remodeling in asthmatic mice by bone marrow mesenchymal stem cells and its mechanism

Objective To investigate the effect of bone marrow mesenchymal stem cells(MSCs)to reverse asthmatic mice airway inflammation and airway remodeling.Methods Forty male BALB/c mice were randomly divided into MSCs control group,MSCs treatment group,asthma model group and normal control group.MSCs were isolated from 4-week-old male mice.The chronic asthma mouse model was made by ovalbumin.The regulatory T cells CD4 + ,CD25 + in peripheral blood were detected by flow cytometry.And to observe the situation of airway remodeling and airway inflammation after inhibition of MSCs.Results Pathological examination showed asthmatic bronchial epithelial mucosa goblet cell hyperplasia,mucosal epithelial shedding,parts of the lumen with inflammatory cell infiltration,airway smooth muscle cell hypertrophy and hyperplasia.There was no airway remodeling and inflammation in the control group and MSCs control group,however there was significantly airway inflammation and airway remodeling phenomenon in MSCs.The CD4 + ,CD25 + regulatory T cells was significantly reduced in asthma model group than in MSCs control group and normal control group(F =12.346,14.528,all P <0.05),and significantly increased in MSCs treatment group compared with asthma group (F =9.438,P <0.05).There was no significant difference between MSCs treatment group,MSCs control group,and normal control group.Conclusions MSCs could reverse airway inflammation and airway remodeling in asthmatic mice by up-regulating the proportion of CD4 + ,CD25 + regulatory T cells.