Slit2/Robo1信号在胃肠道血管畸形发病机制中的作用以及沙利度胺对其表达的影响

Role of Slit2/Robo1 in the Pathogenesis of Gastrointestinal Vascular Malformation and the Effect of Thalidomide on Their Expression

关键词:  胃肠道  血管畸形  沙利度胺  Slit2  Robo1

Key words:  gastrointestinal  vascular malformation  thalidomide  Slit2  Robo1

摘要:

目的 探讨Slit2/Robo1信号在胃肠道血管畸形发病机制中的作用以及沙利度胺对其表达的影响。方法 收集7例胃肠道血管畸形患者血管病变组织与正常黏膜组织，分别检测Slit2，Robo1，VEGF基因和蛋白水平的表达。体外培养原代人脐静脉内皮细胞至对数生长期，同步化后用不同浓度的沙利度胺(50，100，200 mg·L^-1)作用24和48 h后，实时定量PCR法测定处理组与溶剂对照组的Slit2，Robo1，VEGF mRNA表达水平，免疫印迹法测定Slit2，Robo1，VEGF蛋白表达水平。结果 胃肠道血管畸形患者血管病变组织中Slit2，Robo1，VEGF基因及蛋白表达水平显著高于正常黏膜组织。沙利度胺能够明显抑制Slit2，Robo1，VEGF基因与蛋白的表达。结论 Slit2，Robo1可能与胃肠道血管畸形的发病相关，而沙利度胺可抑制其表达，这一作用可能是沙利度胺抑制血管生成，治疗胃肠道血管畸形的机制之一。

Abstract:

OBJECTIVE To study the role of Slit2/Robo1 in the pathogenesis of gastrointestinal vascular malformation (GIVM) and the effect of thalidomide on their expression. METHODS We collected the biopsy specimens of 7 patients with GIVM including the vascular malformation region and normal mucosa region. The expression levels of vascular endothelial growth factor(VEGF), Slit2, Robo1 in patients tissues was measured by Western blot to find out the difference in the mucosa. Then cultured human umbilical vein endothelial cell(HUVEC) and intervened HUVEC with thalidomide of different concentration(50, 100, 200 mg·L^-1) for 24 hours or 48 hours to observe the expression of VEGF, Slit2, Robo1 by real-time PCR and Western blot. RESULTS VEGF, Slit2, Robo1 was strongly expressed in all patients tissues with angiodysplasia lesions, as compared to expression in tissues without angiodysplasia lesions of the same patient. Thalidomide decreased VEGF, Slit2, Robo1 expression, both at the protein and mRNA levels in a dose-dependent manner. CONCLUSION Slit2/Robo1 may play an important role in the pathogenesis of angiodysplasia. Thalidomide can suppress VEGF, Slit2/Robo1 expression. This may be the mechanism of the therapeutic effect of thalidomide on GIVM.