中文摘要：

目的：探讨1-磷酸鞘氨醇（S1P）在高糖诱导血管内皮细胞功能损伤中的作用及其机制。方法：在高糖培养的人主动脉内皮细胞模型中,分别或同时给予S1P、鞘氨醇激酶1抑制剂和Akt抑制剂处理后,观察一氧化氮（NO）、粒细胞-内皮细胞黏附率、细胞间黏附分子1（ICAM-1）蛋白表达、内皮细胞迁移以及Akt/内皮型一氧化氮合酶（e NOS）信号途径的改变。结果：S1P明显降低高糖诱导的内皮细胞培养上清液中NO含量,促进粒细胞与内皮细胞黏附,显著增加内皮细胞ICAM-1蛋白表达,抑制内皮细胞迁移和Akt/eNOS信号通路激活。鞘氨醇激酶1抑制剂减少S1P生成后上述内皮细胞功能指标得以明显改善,Akt/e NOS信号通路恢复激活。结论：S1P促进高糖培养的内皮细胞功能障碍的形成,可能与其抑制Akt/e NOS信号通路激活有关。抑制S1P生成有望成为减轻内皮细胞功能损伤的治疗策略之一。

英文摘要：

AIM： To explore the role of sphingosine 1-phosphate （SIP） in the dysfunction of vascular endo- thelial ceils exposed to high glucose. METHODS： In human aortic endothelial cells cultured under high-glucose （22 mmol/L glucose） medium, nitric oxide （NO） level, polymorphonuclear neutrophil-endothelial cell adhesion rate, protein level of intercellular adhesion molecule-1 （ ICAM-1 ）, migration of endothelial ceils and Akt/endothelial nitric oxide syn- thase （eNOS） pathway activation were observed after SIP, sphingosine kinase-1 inhibitor and/or Akt inhibitor treatments. RESULTS： S1P decreased NO level, increased polymorphonuclear neutrophil adhesive rate, enhanced ICAM-1 protein level, and inhibited migration of endothelial cells and activation of Ak/eNOS pathway in endothelial ceils cultured under high-glucose condition. Sphingosine kinase-I inhibitor , which reduced S1P content, significantly improved the above endo- thelial ceil function indexes and restored the activation of Akt/eNOS pathway. CONCLUSION： S1P promoted high glu- cose-induced dysfunction of endothelial cells probably by inhibiting the activation of Akt/eNOS signal pathway. Targeting SIP is expected to become one of potential treatment strategies to reduce endothelial ceil dysfunction.