雌激素和血管内皮细胞生长因子促进血管瘤增殖的体外实验研究

目的：研究雌二醇(E2)和血管内皮细胞生长因子(VEGF)在促进血管瘤血管内皮细胞(HVEC)增殖中的作用和相互关系，以及4羟基他莫昔芬(4OH—TAM)对该促进作用的影响。方法：取2例雌激素受体阳性的皮肤增生期草莓状血管瘤标本，采用组织块培养法培养HVEC。HVEC原代及传代培养在M199培养液中进行，传至第三代时改用无雌激素培养液IMEM进行干预实验，实验分5组：组1(无干预，为对照组)、组2(加E2)、组3(加VEGF)、组4(加E2和VEGF)、组5(加E，、VEGF和4OH—TAM)。分别在0、3、6、9d进行细胞计数(CC)和流式细胞仪DNA增殖指数(PI)检测。结果例1在第9d时，组2示HVEC轻微增殖，CC和PI分别为组1的1．38倍和1．61倍；组3示CC及PI明显增加，分别为组2的2．10倍和1．61倍；组4示OC及PI的增加更加显著，分别是组3的1．62倍和1．40倍；组5的OC和PI与组1相仿。例2的实验结果与例1相似。结论：体外实验显示雌激素能够轻微促进HVEC增殖；VEGF可明显促进HVEC增殖；而雌激素和VEGF同时存在时，对HVEC的促增殖作用更加显著，二者存在协同作用；他莫昔芬能抑制这种协同促增殖作用。

Synergistic effect of estrogen and VEGF on hemangioma vascular endothelial cell proliferation

Objective To assess the effect of estradiol (E 2),vascular endothelial growth factor (VEGF),and 4OH-tamoxifen (4OH-TAM) on the proliferation of hemangioma vascular endothelial cells (HVEC). Methods Two strawberry hemangiomas with positive estrogen receptor staining from 2 infants (case 1 and 2) were cultured (HVEC). The HVEC of passage 3 were cultured in estrogen-free improved minimum essential medium and divided into 5 groups based on different treatments: group 1,no treatment;group 2,treated with E 2;group 3,treated with VEGF;group 4,treated with both E 2 and VEGF;group 5,treated with E 2,VEGF and TAM. Cell count (CC) and DNA proliferation index (PI) were determined on culture days 0,3,6,and 9.Results On day 9 in case 1,CC and PI were as followed: in group 2, 1.38 and 1.61 times those of group 1,respectively ;in group 3, 2.10 and 1.61 times those of group 2,respectively;in group 4, 1.62 and 1.40 times as high as with group 3,respectively ;in group 5,down to the levels of group 1. The results in case 2 were similar to those in case 1.Conclusions In vitro,the stimulating effect of VEGF on HVEC proliferation is stronger than that of estrogen. Estrogen and VEGF enhance the cell proliferation in a synergistic fashion,which in turn can be inhibited by tamoxifen.