脐血间充质干细胞对肺纤维化大鼠MMP2/TIMP-1的影响

Effects of Cord Blood Mesenchymal Stem Cells on Pulmonary Fibrosis

目的观察脐血间充质干细胞(CB-MSCs)对肺纤维化大鼠MMP2/TIMP-1的影响。方法选取广东省医学实验动物中心提供的36只雄性SD大鼠随机均分为3组,每组各12只。对照C组气管内注入生理盐水0.1 m L,模型M组及治疗T组按5 mg/kg气管内注入博来霉素0.1 m L;造模后T组经尾静脉注射CB-MSCs 106,C组、M组注射生理盐水对照。于第28、42 d分别处死各组大鼠的一半(分别为C1、C2、M1、M2、T1、T2组),留取肺组织测定MMP-2、TIMP-1水平及病理观察、结果 (1)M组大鼠较C组的肺泡结构严重紊乱,大量胶原纤维沉积,并随时间进展,T1、T2组较同期M1、M2组均显著减轻。(2)比较肺纤维化评分、肺泡炎程度,M组较对照C组显著加重,T组较M组明显减轻。(3)C1、C2、M1、M2、T1和T2组大鼠肺组织MMP-2/TIMP-1比值,组间比较差异有统计学意义(P<0.05)。(4)各组大鼠肺组织MMP-2、TIMP-1水平与肺纤维化评分呈正相关(P<0.05)。结论脐血间充质干细胞可通过调节MMP-2/TIMP-1水平延缓肺纤维化进展。

Objective To investigate the effects of cord blood mesenchymal stem cells（ CB-MSCs） on matrix metalloproteinase-2（ MMP-2）/tissue inhibitor of metalloproteinase-1（ TIMP-1） in pulmonary fibrosis rats. Methods 36 male SD rats were randomly and equally divided into 3 groups： control group（ group C） received intratracheal instillation of normal saline（ NS） 0. 1 mL.Model group（ group M） and CB-MSCs treated group（ group T） received intratracheal instillation of bleomycin（ 5 mg/kg in 0. 1 mL NS）. Group C and group M received NS（ 1. 0 mL） via the tail vein,while Group T were treated with cord blood MSCs 106 on the first day. Half of rats in each group were sacrificed respectively on the 28 and 42 day. The pathologic changes and MMP-2/TIMP-1of the lung tissues were investigated. Results（ 1） Alveolar structure was severely in disorder,and massive collagenous fiber was deposited in group M when compared with group C,and ameliorated significantly in group T.（ 2） The scores of pulmonary fibrosis were decreased in group T when compared with group M.（ 3） The levels of MMP-2/TIMP-1 were positively associated with pulmonary alveolitis and fibrosis scores respectively. Conclusion Cord blood MSCs transplantation can suspend the progress of pulmonary fibrosis. The mechanism may be related to improving the imbalance of MMP-2/TIMP-1.