沙利度胺对人脐静脉内皮细胞增殖和血管生成的影响

The effects of thalidomide on proliferation of endothelial cells of human umbilical vein and angiogenesis

目的探讨沙利度胺治疗血管发育不良所致消化道出血的机制。方法体外培养人脐静脉内皮细胞至对数生长期，分为空白对照组、溶剂对照组（二甲基亚砜）和不同浓度（10、20、40、60、80、100μg／ml）沙利度胺组，根据加或不加成纤维细胞生长因子（bFGF，10ng／ml），共分为16组。刺激72h后，MTT法检测细胞增殖情况，酶联免疫吸附法和实时定量PCR法测定血管内皮生长因子（VEGF）、肿瘤坏死因子-α（TNF—α）表达。结果加或不加bFGF刺激，中、高浓度（≥40μg／ml）沙利度胺均能抑制人脐静脉内皮细胞增殖。未加bFGF刺激时，20μg／ml沙利度胺能明显抑制VEGF表达。加bFGF刺激时，10μg／ml沙利度胺即能明显抑制VEGF表达。未检出TNF—α表达。结论体外实验中，沙利度胺能抑制人脐静脉内皮细胞增殖和VEGF表达，从而抑制血管生成，达到治疗血管发育不良所致消化道出血的目的。

Objective To investigate the mechanism and effect of thalidomide on gastrointestinal bleeding of angiodysplasia. Methods The endothelial cells of human umbilical vein were cultured in vitro to exponential phase of growth, then were divided into blank control, solvent control and different concentrations （ 10 - 100 μg/ml） of thalidomide incubated with or without basic fibroblast growth factor （bFGF）. The cell proliferation was measured by MTT assay 72 h after stimulation. The expressions of vascular endothelial growth factor （VEGF） and tumor necrosis factor-α （TNF-α） were detected by ELISA and real time PCR, respectively. Results The proliferation of endothelial cells of human umbilical vein was inhibited by thalidomide （≥40 μg/ml） both in presence or absence of bFGF. The expression of VEGF could be inhibited by 20 μg/ml of thalidomide in the absence of bFGF and 10 μg/ml in the presence of bFGF. No expression of TNF- α was detected. Conclusions The in vitro study reveals that thalidomide can inhibit the proliferation and the expression of VEGF, which may treat gastrointestinal bleeding of angiodysplasia by suppressing the angiogenesis.