瑞舒伐他汀调节血管内皮生长因子促进动脉瘤栓塞后内皮祖细胞的动员

Rosuvastatin Promote Endothelial Progenitor Cells Mobilization after Aneurysm Coiled via Vascular Endothelial Growth Factor Modulation

目的观察大鼠腹主动脉瘤栓塞模型和内皮祖细胞(EPCs)培养中,瑞舒伐他汀对血管内皮生长因子(VEGF)和EPCs的促进和调节作用。方法选取雄性SD大鼠48只,随机分为2组:未用药组(n=24)和瑞舒伐他汀组(n=24)。通过血管移植端侧吻合方法构建腹主动脉瘤栓塞后模型,并经灌胃给予瑞舒伐他汀20 mg·kg-1·d-1治疗。采用流式细胞术检测药物治疗后外周血循环EPCs水平变化并通过ELISA评估外周血VEGF水平。瑞舒伐他汀组大鼠骨髓分离的EPCs,采用MTT方法检测不同剂量瑞舒伐他汀对培养的P2代EPCs活性的影响,划痕实验和成血管实验检测EPCs的功能变化水平;使用定量聚合酶链反应(q PCR)对EPCs分化相关的Ephrin B2和Eph B4表达量进行检测。结果动脉瘤栓塞造模后,瑞舒伐他汀可以在第10天明显提高外周血VEGF水平,并引起第30天时循环EPCs明显提高;经鉴定被0.001μmol·L-1瑞舒伐他汀干预18 h后,表现出明显的促进EPCs活性作用,并显著提升了EPCs的迁移和成管能力;同时q PCR检测表明Ephrin B2表达水平有明显提高。结论瑞舒伐他汀可提升外周血VEGF和EPCs水平,能促进EPCs的活性、迁移和成管能力。

Aim To explore the modulation and promotion of rosuvastatin for vascular endothelial growth factor （VEGF） and endothelial progenitor cells （EPCs） in coiled aneurysm rat model and cultured. Methods Forty-eight adult male Sprague-Dawley rats underwent microsurgery were created the coiled aneurysm models in vivo assay. The rats were treated with rosuvastatin, and the levels of circulating EPCs and VEGF were determined via flow cytometry and ELISA. Rosuvastatin on viability and functioning of Sprague-Dawley rat bone marrow derived EPCs were also explored via MTT, scratch and tube formation assay. The expression levels of EphrinB2 and EphB4 were determined via quantitative polymerase chain reaction. Results After aneurysm coiled, rosuvastatin therapy elevated peripheral VEGF level in the 10th day and EPCs in the 30th day. In vitro assay, 0.001 μmol-L-1 rosuvastatin for 18 h promoted viability, migration and tube formation of EPCs. qPCR showed that expression of EphrinB2 increased after the treatment of rosuvastatin. Conclusion Rosuvastatin increased peripheral blood levels of VEGF and EPCs in coiled