Gadolinium-promoted angiogenesis involves the activation of PKCα/β_2 and MAPKs in human umbilical vein endothelial cells  

氯化钆对人脐静脉内皮细胞体外血管形成能力的影响(英文)

作　　者：万箫[1] 苟宝迪[1] 王夔[1] 

机构地区：[1]北京大学医学部药学院化学生物学系,北京100191

出　　处：《Journal of Chinese Pharmaceutical Sciences》2013年第1期71-76,共6页中国药学（英文版）

基　　金：National Natural Science Foundation of China(Grant No.20637010)

摘　　要：Gadolinium has been widely used as a contrast agent for magnetic resonance imaging in clinical practice. Recently, it was reported that gadolinium is involved in nephrogenic systemic fibrosis, although the exact mechanism by which gadolinium triggers nephrogenic systemic fibrosis remains unclear. In this study, we show that gadolinium chloride （GdC13） induced human umbilical vein endothelial cells （HUVECs） to migrate in Matrigel and tubulogenesis during wound healing. Chick chorioallantoic membrane assay confirmed that GdC13 stimulates angiogenesis. Under the optimal angiogenic concentration of GdC13 （1 0 ~tM）, intracellular calcium concentration and reactive oxygen species generation were elevated. Moreover, western blotting results indicate that in cells treated with GdC13, Ca2＋-dependent PKCa/132 was phosphorylated, and MAPKs pathways were also activated. Taken together, GdC13 has a potential effect on angiogenesis in HUVECs, and the possible mechanisms may involve oxidative stress and calcium-related signalin~ pathways.钆离子的配合物作为核磁共振造影增强剂在临床诊断中得到广泛应用。晚期肾病患者多次大剂量使用钆造影剂后,可能发生肾源性系统纤维化,目前其确切机理还不清楚。我们考察了不同浓度的氯化钆对人脐静脉内皮细胞的迁移和成管能力的影响;在鸡胚尿囊膜模型中,10μM氯化钆诱导生成更多的新生血管。这些实验结果表明氯化钆具有促进人脐静脉内皮细胞体外血管形成能力,这种作用涉及细胞内活性氧物种和钙离子水平的变化,以及PKCα/β2和MAPKs信号通路的激活。该研究为探索钆造影剂和肾源性系统纤维化之间的关系提供了新线索。

关 键 词：Gadolinium chloride ANGIOGENESIS Reactive oxygen species Signaling pathways Human umbilical vein endothelial cells 

分 类 号：R363[医药卫生—病理学]