BMSCs条件培养液对博来霉素诱导的肺纤维化大鼠肺组织MMP-9/TIMP-1的影响

Effects of BMSCs conditioned medium on ratio of MMP-9 to TIMP-1 in lung tissues of rats with pulmonary fibrosis induced by bleomycin

目的观察骨髓间充质干细胞(BMSCs)条件培养液对大鼠肺纤维化的影响。方法 50只SD大鼠随机分为健康对照组、模型组、治疗组(A、B和C)。模型组和各治疗组经气管内注入博莱霉素(5 mg/kg),对照组注入生理盐水。次日,模型组经尾静脉注入DMEM/F-12浓缩培养基,各治疗组经尾静脉分别注入不同数量BMSCs条件培养液。20 d后取肺组织进行苏木精-伊红(H-E)及Masson染色;测肺组织羟脯氨酸(HYP)含量,MMP-9 mRNA、TIMP-1 mRNA表达变化以及肺组织匀浆中MMP-9、TIMP-1蛋白含量。结果与模型组相比,各治疗组肺泡炎症反应程度、肺纤维化程度及HYP含量均有所减轻。治疗组肺组织MMP-9 mRNA含量、肺组织匀浆中MMP-9蛋白含量与MMP-9/TIMP-1蛋白含量比值均较模型组、对照组升高。结论 BMSCs条件培养液可通过促进MMP-9及MMP-9/TIMP-1的升高减轻博来霉素诱导的肺泡炎和肺纤维化。

Objective To observe the effects of bone marrow-derived meschymal stem cells（BMSCs）conditioned medium on pulmonary fibrosis of rats.Methods Fifty SD rats were randomly divided into normal control group,model group,and treatment group（A,B,and C）.Rats of the model group and treatment groups were intratracheally perfused with bleomycin（5 mg/kg） and rats of the control group were intratracheally perfused with normal saline.Rats of the model group were injected with DMEM /F-12 concentrated culture medium via caudal vein on the next day.Rats of treatment groups were injected with different volumes of BMSCs conditioned medium via caudal vein.Lung tissues of rats were harvested after 20 d and hematoxylineosin（H-E） staining and Masson staining were performed.The hydroxyproline（HYP） level and changes of mRNA expressions of MMP-9 and TIMP-1 in lung tissues and levels of MMP-9 and TIMP-1 proteins in lung tissue homogenate were detected.Results Compared with the model group,alveolitis and pulmonary fibrosis of three treatment groups alleviated and the level of HYP decreased.The mRNA level of MMP-9 in lung tissues and the protein level of MMP-9 and the ratio of MMP-9 to TIMP-1 in lung tissue homogenate of treatment groups were higher than those of the model group and control group.Conclusion The BMSCs conditioned medium can alleviate alveolitis and pulmonary fibrosis induced by bleomycin via increasing the level of MMP-9and the ratio of MMP-9 to TIMP-1.