摘要
目的探讨前列腺素E1（PGE1）促进人脐静脉内皮细胞（HUVEC）增生、迁移及其机制。方法应用免疫印迹，酶联免疫吸附试验和其他细胞功能试验检测PGE1对HUVEC的作用及其机制；应用免疫印迹检测大鼠主动脉血管平滑肌细胞（VSMC）的血管内皮生长因子（VEGF）表达。结果PGE1刺激HUVEC VEGF表达、ERK和p38磷酸化；贝伐单抗中和PGE1诱导的HUVEC条件培养液内的VEGF，抑制细胞增生和迁移以及类毛细血管形成；PD98059或SB203580，均抑制PGE1诱导的HUVEC表达VEGF、HUVEC增生和迁移；此外，H89或Rp—cAMP抑制PGE1诱导的VSMC VEGF的表达。结论PGE1通过VEGF诱导内皮细胞增生、迁移和类毛细血管形成的机制为它在动脉缺血性疾病和其他相关疾病的应用进一步提供了理论支持。
Objective To investigate the mechanism（s） that prostaglandin E1 （PGE1） promotes human umbilical vein endothelial cell （HUVEC）proliferation and migration. Methods Western blot, enzyme linked immunosorbent assay, cell proliferation and cell migration tests, and tube formation were used for analyzing the roles and mechanisms of PGE1 on HUVEC ;Western blot was used for analyzing the effects of PGE1 on the expression of vascular endothelial growth factor （VEGF） in rat aortic vascular smooth muscle cells （VSMC）. Results PGE1 significantly increased VEGF expression of HUVEC in time and a dose dependent manner with concomitantly increased HUVEC proliferation; treatment of HUVEC with Bevacizumab apparently suppressed PGEl-stimulated VEGF expression, which led to decreased tube formation, reduced cell proliferation and migration by 41% and 38%, respectively, compared with PGE1 treatment alone ; PGE1 time-dependently induced both phosphorylation of ERK and p38 in HUVEC, whereas ERK inhibitor, PD98059, or p38 inhibitor, SB203580, blocked PGEl-induced VEGF expression of HUVEC, resulting in dramatically suppression of HUVEC proliferation and migration compared with PGE1 treatment alone （60% and 55% by PD98059, 62% and 51% by SB203580, respectively）; in addition, cAMP-dependent protein kinase A inhibitor, H89 or Rp-cAMP blocked PGEl-induced VEGF expression in VSMC. Conclusion PGE1 promotion of proliferation, migration and tube formation of HUVEC via VEGF further provides a novel theoretical support in efficacy of PGE1 treatment of critical limb ischemia and other related diseases.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2013年第3期222-225,共4页
National Medical Journal of China
关键词
前列腺素E1
内皮细胞
血管内皮生长因子
增生
迁移
Prostaglandin El
Endothelial cell
Vascular endothelial growth factor
Proliferation
Migration
