雷公藤内酯醇抑制血管内皮细胞生长因子的表达与合成

Triptolide inhibits vascular endothelial growth factor expression and production by endothelial cells

目的 探讨雷公藤内酯醇对血管内皮细胞生长因子 (VEGF)mRNA表达及VEGF合成与分泌的影响 ,进一步探讨雷公藤内酯醇降低肾小球肾炎患者尿蛋白的作用机制。方法 以人内皮细胞系ECV 30 4为研究对象 ,利用逆转录 聚合酶链反应 (RT PCR)、流式细胞仪、酶联免疫吸附法(ELISA)检测不同剂量雷公藤内酯醇对佛波脂 (PMA)诱导的内皮细胞VEGFmRNA表达及VEGF合成与分泌的影响 ,并采用RT PCR检测雷公藤内酯醇对内皮细胞c jun/c fosmRNA表达的影响。结果雷公藤内酯醇可以抑制PMA诱导的内皮细胞VEGFmRNA表达及VEGF合成与分泌 ,并呈剂量依赖性。同样 ,雷公藤内酯醇剂量依赖性抑制PMA诱导的内皮细胞c jun/c fosmRNA的表达。结论 雷公藤内酯醇抑制内皮细胞VEGFmRNA表达及VEGF合成与分泌可能是其雷公藤内酯醇降低肾小球肾炎患者尿蛋白的作用机制之一。雷公藤内酯醇可能通过影响转录因子AP

Objective To investigate the effect of triptolide on vascular endothelial growth factor (VEGF) expression and secretion by endothelial cells, and explore the mechanism of anti proteinuric effect of triptolide on glomerular nephritis. Method A human umbilical endothelium derived cell line (ECV 304)from American Type Culture Collection(ATCC) was used in this study. The effects of triptolide on VEGF mRNA expression, and intracellular protein production and secretion induced by PMA were measured by RT PCR, flow cytometry and enzyme linked immunosorbent assay (ELISA). The effects of triptolide on endothelial c jun/c fos mRNA expression were investigated by RT PCR. Result 100 ng/ml PMA significantly increased VEGF mRNA expression, intracellular production and secretion of VEGF in endothelial cells, while triptolide inhibited the effects of PMA in a dose dependent manner. Moreover, triptolide dose dependently inhibited endothelial c jun/c fos mRNA expression. Conclusion Triptolide is a potent inhibitor of VEGF expression and production, suggesting that the inhibitory influence of triptolide on VEGF expression and production may be one of the mechanisms underlying its anti proteinuric effect on glomerular nephritis. Triptolide might inhibit VEGF expression and production by interfering with transcription factor AP 1 formation.