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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。
Objective To observe the effects of rosuvastatin on vascular endothelial growth factor (VEGF) and EPCs in rat models of abdominal aortic aneurysm embolism and endothelial progenitor cells (EPCs). Methods Forty eight male Sprague Dawley rats were randomly divided into 2 groups: untreated group (n = 24) and rosuvastatin group (n = 24). The model of abdominal aortic aneurysm embolization was established by end-to-side anastomosis of vascular grafts and treated with rosuvastatin 20 mg · kg-1 · d-1 by intragastric administration. Flow cytometry was used to detect the level of EPCs in peripheral blood after drug treatment and the level of VEGF in peripheral blood was evaluated by ELISA. The EPCs isolated from the rat bone marrow of rosuvastatin group were assayed by MTT assay. The effects of different dosages of rosuvastatin on the activity of EPCs on passage P2 were detected. Scratch and angiogenesis assays were used to detect the changes of EPCs activity. Chain reaction (q PCR) was used to detect the expression of Ephrin B2 and Eph B4 in EPCs. Results Rosuvastatin could significantly increase the level of VEGF in peripheral blood on day 10 after induced by embolization of aortic aneurysm, and significantly increased the circulating EPCs on the 30th day. It was identified that rosuvastatin was inhibited by 0.001μmol·L-1 rosuvastatin for 18 hours Afterwards, EPCs showed obvious activity of promoting EPCs, and significantly enhanced the migration and tube formation ability of EPCs. At the same time, q PCR detection showed that the expression of Ephrin B2 was significantly increased. Conclusion Rosuvastatin can enhance the levels of VEGF and EPCs in peripheral blood and promote the activity, migration and tube formation of EPCs.