骨髓间充质干细胞抑制大鼠肺纤维化的作用机制

发布时间：2018-06-10 04:17

本文选题：肺纤维化 + 间充质干细胞　；参考：《华中科技大学学报(医学版)》2014年03期

【摘要】：目的观察骨髓间充质干细胞(MSCs)对大鼠肺纤维化抑制作用的机制。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4组(每组12只):正常对照组(气管内注入生理盐水)、模型组(气管内注入博莱霉素)、MSCs治疗早期组(造模后立即给予尾静脉注射MSCs)、MSCs治疗晚期组(造模后14d给予尾静脉注射MSCs),气管内注入博莱霉素用量为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1.0×106/mL DMEM培养液1mL。于第28天统一处死大鼠后取肺组织,肺组织病理切片行苏木精-伊红(HE)染色及Masson染色观察肺部炎症和纤维化情况,Western blot法检测肺组织转化生长因子-β1(TGF-β1)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶组织抑制剂-1(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差异无统计学意义。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差异无统计学意义。结论骨髓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]:Objective to investigate the inhibitory mechanism of bone marrow mesenchymal stem cells (MSCs) on pulmonary fibrosis in rats. Methods isolated and cultured in vitro, Bone marrow MSCs.SD experimental rats of 4-week-old SD rats were randomly divided into 4 groups (12 rats in each group): normal control group (normal saline injection in trachea) and model group (treated early with bleomycin MSCs in trachea). The rats in the late stage group were treated with MSCs by tail vein injection (14 days after the model was made). The dose of bleomycin in trachea was 5 mg / kg, and the normal control group was injected with the same volume of normal saline. The dose of MSCs was 1.0 脳 106 / mL DMEM culture medium (1 mL / mL). On the 28th day, the rats were killed and the lung tissue was removed. Lung tissue sections were stained with hematoxylin eosin (HEH) and Masson staining. The expression of transforming growth factor-尾 1 (TGF- 尾 1), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase inhibitor-1 (TIMP-1) in lung tissue were detected by blot. Results 1 MSCs were isolated and cultured successfully and the alveolitis and pulmonary fibrosis degree of model group 2 were significantly aggravated than that of normal control group. The alveolitis and pulmonary fibrosis degree of MSCs in early treatment group was significantly reduced than that in model group. The degree of inflammation and pulmonary fibrosis was not different from 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. The expression of TGF- 尾 1 and TIMP-1 protein in the MSCs treatment group was significantly lower than that in the model group, and the expression of TGF- 尾 1 and TIMP-1 protein in the model group was significantly lower than that in the model group. The difference was not statistically significant. Conclusion Bone marrow MSCs can inhibit bleomycin induced pulmonary fibrosis, and the intervention effect of MSCs in the early stage of lung injury is better. The mechanism may be to reduce the expression of TGF- 尾 1 protein and regulate the balance between MMP-2 and TIMP-1.
【作者单位】：华中科技大学同济医学院附属梨园医院呼吸内科;
【基金】：湖北省自然科学基金资助项目(No.2010CHB01100)
【分类号】：R563.9

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