急性心肌梗死患者可溶性Tie-2的检测及其对血管新生作用的研究

Assay of Soluble Angiopoietin Receptor Tie-2 in Patients with Acute Myocardial Infarction and Its Effects on Angiogenesis

目的探讨急性心肌梗死患者血清中血管生成素-1(Ang-1)及可溶性酪氨酸激酶受体Tie-2(sTie-2)的浓度变化及重组人可溶性Tie-2/Fc嵌合体对内皮细胞存活及管状形成的作用。方法ELISA法检测急性心肌梗死患者(AM I组,入院当天、发病48、72 h及1周时分别取血)和健康对照组血清中VEGF、Ang-1及sTie-2浓度变化。体外培养人脐静脉内皮细胞(HUVEC),观察重组Ang-1及Tie-2/Fc对内皮细胞存活及管状形成的影响。结果AM I组VEGF及Ang-1浓度与对照组相比无显著差异。AM I组sTie-2浓度显著高于对照组,其中以发病48 h的浓度最高,男性血清sTie-2浓度显著高于女性。重组Ang-1能够协同VEGF促进内皮细胞管状形成,重组Tie-2/Fc诱导内皮细胞凋亡,抑制管状形成。结论AM I时血清sTie-2浓度升高并随病程发展而变化,Tie-2/Fc抑制管状形成可能提示AM I患者急性期存在血管新生减低。

Objective （1） To study the potential role of angiopoietin-1 （Ang-1） and soluble Tie-2 （sTie-2） in patients with AMI, a condition whose pathophysiology also involves angiogenesis. （2） To study the effects of recombinant human Ang-1 and Tie-2/Fc chimera on angiogenesis of endothelial cells. Methods Levels of VEGF, Ang-1 and sTie-2 in 27 patients with AMI at different time after administration and 28 healthy controls were measured by ELISA. HUVECs were seeded in three-dimensional fibrin gel and treated with recombinant Ang-1 or Tie-2/Fc chimera. Tube formation area was measured after 48 hours. Results Levels of VEGF and Ang-1 have no difference between two groups. Median level of sTie-2 was significantly higher in the AMI patients than controls. The maximum levels of sTie-2 appeared at 48 hours after onset of AMI. Male has higher concentration of sTie-2 than female. Ang-1 enhanced the pro-angiogenesis of VEGF in vitro. Tie-2/Fc increased apoptosis rate of HUVEC and inhibited tube formation significantly. Conclusion The level of sTie- 2 increased in AMI patients, and the maximum level appeared at 48h after onset of AMI. The effects of Tie-2/ Fc on tube formation in vitro may indicate that angiogenesis may be inhibited in acute phase of AMI.