骨髓间充质干细胞对肺纤维化大鼠基质金属蛋白酶及其抑制剂的影响

发布时间：2018-06-29 11:39

本文选题：肺纤维化 + 间充质干细胞　；参考：《华中科技大学》2013年硕士论文

【摘要】：目的：观察骨髓间充质干细胞（MSCs）移植对博莱霉素（BLM）诱导的肺纤维化大鼠基质金属蛋白酶及其抑制剂的影响，探讨其对肺纤维化大鼠的作用机制。方法：体外分离、培养、纯化4周龄SD大鼠的骨髓MSCs。SD实验大鼠随机分为四组（每组12只）：正常对照组（气管内注入生理盐水）、模型组（气管内注入BLM）、MSCs治疗早期组（BLM造模后立即给予尾静脉注射MSCs）、MSCs治疗晚期组（BLM造模后14天给予尾静脉注射MSCs），气管内注入BLM用量为5mg／kg，正常对照组注入等体积生理盐水，尾静脉注射MSCs用量为MSCs1.0×106／ml DMEM培养液1ml。于第28天统一处死大鼠后取肺组织，，肺组织病理切片行HE染色及Masson染色观察肺部炎症和纤维化情况，蛋白印迹法（Western blot）检测肺组织TGF-β1、MMP-2、TIMP-1蛋白表达量。结果：①成功分离培养MSCs并鉴定。②模型组肺泡炎和肺纤维化程度较正常对照组明显加重,MSCs治疗早期组肺泡炎和肺纤维化程度较模型组显著减轻, MSCs治疗晚期组肺泡炎和肺纤维化程度与模型组比较无显著差异。③模型组TGF-β1、TIMP-1蛋白表达较正常对照组显著增加,MSCs治疗早期组和MSCs晚期组TGF-β1、TIMP-1蛋白表达较模型组显著减少，MMP-2蛋白表达在各组大鼠间无显著差异。结论：骨髓间充质干细胞（MSCs）可抑制博莱霉素诱导的肺纤维化并且在肺损伤早期给予MSCs干预的疗效更好，其机制可能为降低TGF-β1蛋白的表达，调节MMP-2与TIMP-1之间的平衡。
[Abstract]:Aim: to investigate the effects of bone marrow mesenchymal stem cells (MSCs) transplantation on matrix metalloproteinases and their inhibitors in bleomycin (BLM)-induced pulmonary fibrosis rats. Methods: isolated and cultured in vitro, Bone marrow MSCs.SD rats of 4-week-old SD rats were randomly divided into four groups (12 rats in each group): normal control group (normal saline injected into trachea), model group (intratracheal injection of BLM) and early treatment group (BLM). MSCs were injected intravenously into the trachea for 5 mg / kg in the late stage group (14 days after BLM model), and the same volume of normal saline was injected into the normal control group. The dosage of MSCs was 1.0 脳 106/ml DMEM. On the 28th day, the lung tissue was taken out and the lung tissue was stained with HE and Masson staining. The expression of TGF- 尾 1, MMP-2 and TIMP-1 in lung tissue was detected by Western blot. Results MSCs were isolated and cultured successfully and the alveolitis and pulmonary fibrosis degree in model group .2 were significantly aggravated than those in normal control group. The alveolitis and pulmonary fibrosis degree of MSCs in early treatment group was significantly less than that in model group, and that in the late stage of MSCs treatment group was significantly lower than that in the model group. There was no significant difference in the degree of alveolitis and pulmonary fibrosis between the model group and the model group. 3. The expression of TGF- 尾 1 and TIMP-1 protein in the model group was significantly higher than that in the normal control group, and the expression of TGF- 尾 1 and TIMP-1 protein in the early treatment group and the late MSCs group in the model group was significantly lower than that in the model group. There was no significant difference between each group. Conclusion: bone marrow mesenchymal stem cells (MSCs) can inhibit bleomycin-induced pulmonary fibrosis and interfere with MSCs in the early stage of lung injury. The mechanism may be to reduce the expression of TGF- 尾 1 protein and regulate the balance between MMP-2 and TIMP-1.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R563

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