丹参酮ⅡA磺酸钠在缺血性斑马鱼模型中的促血管新生作用

摘要

Objective:To investigate the angiogenic effect and potential mechanism of sodium tanshinone ⅡA sulfonate (Tan ⅡA) in ischemic zebrafish model.Methods:Vascular endothelial growth factor receptor kinase inhibitor (VRKI) was used to induce vascular injury in zebrafish model.Then the ischemic zebrafish model was treated with 50, 100, 200 μmol/L Tan ⅡA, respectively.The effects of Tan ⅡA on ischemic zebrafish subintestinal veins (SIVs) and intersegmental vessels (ISVs) were observed.Meanwhile, the expression changes of three vascular endothelial growth factor (VEGF) signaling pathway-related genes (flt-1, flk-1A, flk-1B) were detected by real-time PCR.Results:In VRKI-induced vascular injury zebrafish model, Tan ⅡA gradually restored ISVs and SIVs in a concentration-dependent manner, reversed the down-regulated expressions of three key VEGF signaling pathway-related genes (flt-1, flk-1A, flk-1B), and promoted angiogenesis.Conclusions:In the ischemic zebrafish model, Tan ⅡA plays a role in angiogenesis and vascular protection by regulating VEGF signaling pathway.%目的:观察丹参酮ⅡA磺酸钠 (Tan ⅡA)对缺血性斑马鱼模型的促血管新生作用及其潜在机制.方法:用内皮细胞生长因子受体酪氨酸激酶抑制剂(VRKI)诱导血管损伤斑马鱼模型,分别予以50、100、200 μmol/L的Tan ⅡA处理.观察Tan ⅡA在上述浓度下对缺血性斑马鱼肠下静脉血管(SIVs)和节间血管(ISVs)的影响,并利用real-time PCR技术检测flt-1、flk-1A (kdrl)、flk-1B(kdr)3个调节血管内皮生长因子(vascular endothelial growth factor ,VEGF)信号通路相关基因的表达变化. 结果:在VRKI诱导的血管损伤斑马鱼模型中,Tan ⅡA呈浓度依赖性地逐渐恢复ISVs和SIVs血管;通过VEGF通路上的相关基因[flt-1、flk-1A (kdrl)、flk-1B(kdr)]进行调控. 结论:在缺血性斑马鱼模型中,Tan ⅡA可通过VEGF信号通路发挥其促血管新生和保护血管作用.