人胎盘间充质干细胞对小鼠肺纤维化的影响及机制

摘要

目的 观察人胎盘间充质干细胞对小鼠肺纤维化的影响,并探讨其作用机制.方法 采用组织块贴壁法分离并体外培养人胎盘间充质干细胞.将30只C57BL/6小鼠随机均分为观察组、对照组,均给予气管内注入博来霉素8.5 mg/kg建立肺纤维化模型.造模成功后,观察组尾静脉输注体外培养的人胎盘间充质干细胞0.3 mL(细胞数为1.0×106个),对照组注射等量生理盐水,1次/d,连续注射3天;处死小鼠,取肺组织,检测肺组织羟脯氨酸含量,采用Western blotting法检测肺组织血管内皮生长因子(VEGF)、内皮素1(ET-1)和血管生成素2(Ang-2)蛋白.结果 观察组肺组织羟脯氨酸含量为(5.76±0.13)μg/mL,对照组为(8.13±0.87)μg/mL,两组比较P＜0.01.观察组肺组织VEGF的相对表达量为52.7±4.7、ET-1为68.1±5.4、Ang-2为59.6±2.8,均较对照组(100)降低(P均＜0.05).结论 人胎盘间充质干细胞可抑制小鼠肺组织纤维化形成;降低肺组织VEGF、ET-1和Ang-2表达可能是其作用机制.%Objective To observe the effect of placenta-derived mesenchymal stem cells on the pulmonary fibrosis in mice and to explore its mechanism.Methods Human placenta-derived mesenchymal stem cells were isolated and cultured in vitro by tissue explants adherent method.Thirty C57BL/6 mice were randomly divided into the observation group and the control group, and all mice were injected with 8.5 mg/kg to establish the model of pulmonary fibrosis.After the models were successful established, mice in the observation group received intravenous injection of placenta-derived mesenchymal stem cells 0.3 mL (cell number of 1.0 ×106), and mice in the control group were injected with the same amount of nor-mal saline, once a day for 3 days.Then, the mice were killed to collect the lung tissues to determine the content of hydroxyproline.The expression of vascular endothelial growth factor ( VEGF ) , endothelin 1 ( ET-1 ) and angiogenin 2 ( Ang-2) proteins was determined by Western blotting.Results The hydroxyproline contents in the lung tissue of observa-tion group and control group were respectively (5.76 ±0.13) μ/mL and (8.13 ±0.87) μg/mL, and significant difference was found between the two groups (P＜0.01).The expression of VEGF, ET-1 and Ang-2 in the lung tissues of the obser-vation group was respectively 52.7 ±4.7, 68.1 ±5.4 and 59.6 ±2.8, which was all lower than that of the control group (all P＜0.05).Conclusion Placenta-derived mesenchymal stem cells can inhibit the formation of pulmonary fibrosis and its mechanism may be related with the decreased expression of VEGF, ET-1 and Ang-2 protein in lung tissue.