摘要
为探讨λ-卡拉胶寡糖体外对血管生成的抑制作用,采用鸡胚尿囊膜模型(CAM)观察λ-卡拉胶寡糖对CAM血管发育的抑制,发现该寡糖可明显抑制CAM微血管生成,在200μg.egg-1时,抑制率达54.90%。随后采用MTT法测定λ-卡拉胶寡糖对人脐静脉内皮细胞(HUVEC)增殖的影响,发现该寡糖的细胞毒作用在不同的细胞间具有选择性,对HUVEC的抑制最强,高浓度时(1 mg.mL-1)能明显抑制其增殖,但低浓度(<250μg.mL-1)对细胞几乎无毒。对寡糖的细胞迁移和侵袭抑制作用进行检测,并测定其对HUVEC表达基质金属蛋白酶-2(MMP-2)的影响。结果表明,λ-卡拉胶寡糖能有效减缓HUVEC的迁移、侵袭能力,并具有抑制HUVEC中MMP-2表达的作用。该研究说明λ-卡拉胶寡糖通过抑制内皮细胞的增殖、细胞侵袭和迁移达到血管生成抑制的作用。
This study was designed to evaluate the inhibition effect of λ-carrageenan oligosaccharides on neovascularization in vitro by chick chorioallantoic membrane （CAM） model and human umbilical vein endothelial cell （HUVEC）. λ-Carrageenan oligosaccharides caused a dose-dependent decrease of the vascular density of CAM, and adversely affected capillary plexus formation. At a high concentration of 1 mg·mL^-1, this compound inhibited the endothelial cell proliferation, while low concentration of λ- carrageenan oligosaccharides （ 〈250 μg·mL^-1） affected the cell survival slightly （ 〉 95% ）. Different cytotoxic sensitivity of λ-carrageenan oligosaccharides in three kinds of cells was observed, of which HUVEC is the most sensitive to this oligosaccharides. The inhibitory action of λ-carrageenan oligosaccharides on the endothelial cell invasion and migration was also observed at relatively low concentration （150- 300μg· mL^-1） through down-regulation of intracellular matrix metalloproteinases-2 （MMP-2） expression on endothelial cells. Current observations demonstrated that λ-carrageenan oligosaccharides are potential angiogenesis inhibitor with combined effects of inhibiting invasion, migration and proliferation.
出处
《药学学报》
CAS
CSCD
北大核心
2007年第6期595-600,共6页
Acta Pharmaceutica Sinica
基金
浙江省教育厅项目(20051693)
浙江省自然科学基金资助项目(Y506132)
关键词
Λ-卡拉胶
寡糖
血管生成
鸡胚尿囊膜
脐静脉内皮细胞
λ-carrageenan
oligosaccharides
angiogenesis
chick chorioallantoic membrane
umbilical vein endothelial cell
作者简介
通讯作者Tel／Fax：86-574-87600458．E-mail：chenhaimin@nbu．edu．cn.
