3种姜黄色素抗血管生成及相关因子表达作用研究

Study on anti-angiogenesis effect of three curcumin pigments and expression of their relevant factors

为了解3种姜黄色素(姜黄色素、一脱甲氧基姜黄素、二脱甲氧基姜黄素)体外抗血管生成作用。该研究检测了3种姜黄色素对OX-LDL诱导的人脐静脉内皮细胞HUVEC增殖的抑制作用;对HUVEC细胞迁移的影响;鸡胚绒毛尿囊膜(CAM)法观察姜黄色素对血管生成作用;RT-PCR检测HUVEC细胞生长因子VEGF的表达;RT-PCR检测HUVEC细胞黏附因子ICAM-1,VCAM-1的影响。结果发现3种姜黄色素在4,8,16 mg·L-1剂量范围内,对OX-LDL诱导的HUVEC细胞增殖都有抑制作用,且抑制效果呈剂量依赖关系。姜黄素对HUVEC细胞增殖的作用大于其他2个衍生物(P<0.01)。3种姜黄色素都能抑制HUVEC细胞的迁移、抑制鸡胚绒毛尿囊膜(CAM)血管生成。中,高剂量姜黄素的迁移抑制率大于一脱甲氧基姜黄素、二脱甲氧基姜黄素(P<0.01)。3种姜黄色素都能下调VEGF,ICAM-1的表达,对VEGF下调作用姜黄素比一脱甲氧基姜黄素、二脱甲氧基姜黄素明显(P<0.01);二脱甲氧基姜黄素对ICAM-1的下调作用最明显(P<0.01);三者对VCAM-1的表达作用不明显,二脱甲氧基姜黄素有下调作用(P<0.05)。该研究显示3种姜黄素均有抗血管生成作用,抑制内皮细胞增殖和迁移,下调内皮细胞生长因子VEGF和黏附分子ICAM-1的表达可能是其作用的机制。

To study the in vitro anti-angiogenesis effect of three curcumin pigments（ curcumin, demethoxycurcumin, bisdemethoxy- curcumin）. In the study, the inhibitory effect of the three curcumin pigments on proliferation of HUVEC cells induced by OX-LDL and the effect on migration of HUVEC cells were detected. The effect on neovascularization was observed by chorioallantoic membrane （CAM） test. The effect on cell adhesion factors ICAM-1 and VCAM-1 of HUVECs were tested by Real-time RT-PCR. It was found that the three cur- cumins could inhibit the proliferation of HUVEC cells induced by OX-LDL within the dosage range 4, 8, 16 mg·L^-1 , with a dose-depend- ence. The proliferative effect of curcumins on HUVECs was greater than the other two derivatives （P 〈0.01 ）. All of the three curcumin pig- ments inhibited the migration of HUVEC cells and the angiogenesis of chick chorioallantoic membrane （CAM）. The migration inhibition rate of curcumins at middle and high concentrations was greater than the other two （P 〈0. 01 ）. All of the three curcumin could down-regulate the expression of VEGF and ICAM-1, and curcumins showed more obvious effect in down-regulating VEGF than demethoxycurcumin and bisde- methoxycurcumin（P 〈0. 01 ）; Bisdemethoxycurcumin showed the most significant effect in down-regulating ICAM-1 （P 〈 0. 01 ）. All of the three showed no remarkable effect on expression of VCAM-1, and only bisdemethoxycurcumin showed the down-regulating effect（P 〈0.05）. According to the findings, all of the three curcumin pigments could resist angiogenesis by inhibiting proliferation and migration of endothelial cells and down-regulating the expression of VEGF and adhesion molecules ICAM-1.