应用药理麦冬多糖通过诱导S1P、bFGF表达保护缺血心肌生存及促进血管生成作用.docVIP

麦冬多糖通过S1P、bFGF表达保护生存及促进血管生成作用王硕1徐德生1，冯怡1*，丁侃2* (1．上海中医药大学，上海201203；2．上海药物研究所，上海201203) 摘要1－磷酸鞘氨醇/Akt/ERK信号通路被认为同缺血的发生及治疗密切相关。本实验研究S1P/Akt/ERK信号通路麦冬MDG-1抗心肌缺血作用中的角色，以阐明MDG-1抗缺血损伤的作用机制冠状动脉结扎致大鼠急性心肌缺血（梗塞）实验模拟缺血过程的OGD（氧气和糖剥夺）条件MDG-1的细胞保护作用Western blotting实验，研究MDG-1对相关信号通路的调节作用。结果 MDG-1具有抗心肌缺血损伤作用人微血管内皮细胞（HMEC-1）促进HMEC-1细胞迁移和形成管腔结构上调鞘氨醇激酶(SPHK1)，1－磷酸鞘氨醇受体1(S1P1)和碱性成纤维细胞生长因子(bFGF)表达上调SPHK1和S1P1蛋白表达，并且可以诱导Akt和ERK磷酸化。MDG-1具有抗心肌缺血损伤作用作用机理可能是激活S1P/Akt/ERK信号通路对缺血区域细胞起到保护作用，促进bFGF诱导的血管生成。 1－磷酸鞘氨醇碱性成纤维细胞生长因子Polysaccharides, MDG-1, induces S1P and bFGF expression and augments survival and angiogenesis in the ischemic heart Shuo Wang1, De-Sheng Xu1, Yi Feng1* and Kan Ding2*（1Department of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203; 2Glycochemistry Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203） Abstract: Objective Sphingosine-1-phosphate (S1P)/Akt/ERK signal pathway plays a vital role in survival, anti-apoptosis, migration and tube formation, which is strongly linked to ischemia. The present study investigated the anti-ischemic effect of a polysaccharide from O. japonicus (MDG-1) and the possible mechanism involved with S1P/Akt/ERK signal pathway. Methods The cell protective effect of MDG-1 was measured by coronary artery ligation and OGD induced ischemia. The proangiogenesis effect of MDG-1 was tested by scratch wound migration and tube formation. The intracellular signaling pathways involved in the anti-ischemic effect of MDG-1 were examined by Angiogenesis Antibody Array and Western blotting. Results MDG-1 could remarkably protect myocardial ischemia induced by coronary artery ligation in rats. Besides, it could also prevent HMEC-1 cells from death induced by Oxygen Glucose Deprivation (OGD). Moreover, MDG-1 exhibited a robust effect on tube formation, migration and the secretion of basic fibroblast growth factor (bFGF) levels of HMEC-1 cells. MDG-1 could up-regulate the expression of s