Resveratrol inhibits the release of soluble fms-like tyrosine kinase (sFlt-1) from human placenta
Resveratrol inhibits the release of soluble fms-like tyrosine kinase (sFlt-1) from human placenta
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DOI：
10.1016/j.ajog.2011.11.010
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发表时间：
2012-03-01
影响因子：
9.8
通讯作者：
Ahmed, Asif
中科院分区：
文献类型：
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作者：
Cudmore, Melissa J.;Ramma, Wenda;Ahmed, Asif
目的：可溶性血管内皮生长因子受体-1（sFlt-1）是子痫前期发病的关键因素。白藜芦醇是一种植物抗毒素，具有抗氧化和心脏保护作用。研究设计：将人脐静脉内皮细胞、转化的人滋养层-8（HTR/SVneo）-8/SVneo滋养层细胞或胎盘外植体与细胞因子和/或白藜芦醇一起孵育。通过酶联免疫吸附试验和细胞蛋白用于Western blotting.Results：白藜芦醇抑制姜黄素诱导的正常胎盘组织和先兆子痫胎盘组织sFlt-1的释放。用白藜芦醇预孵育人脐静脉内皮细胞或HTR-8/SVneo细胞可消除sFlt-1的释放。结论：白藜芦醇能抑制sFlt-1的释放，上调血红素氧合酶-1的表达，抑制血管内皮生长因子受体-1基因的表达，并能抑制血管内皮生长因子受体-1基因的表达。因此，可能提供先兆子痫的治疗潜力。
OBJECTIVE: Soluble vascular endothelial growth factor receptor-1 (also know as soluble fms-like tyrosine kinase [sFlt]-1) is a key causative factor of preeclampsia. Resveratrol, a plant phytoalexin, has antiinflammatory and cardioprotective properties. We sought to determine the effect of resveratrol on sFlt-1 release.STUDY DESIGN: Human umbilical vein endothelial cells, transformed human trophoblast-8 (HTR/SVneo)-8/SVneo trophoblast cells, or placental explants were incubated with cytokines and/or resveratrol. Conditioned media were assayed for sFlt-1 by enzyme-linked immunosorbent assay and cell proteins used for Western blotting.RESULTS: Resveratrol inhibited cytokine-induced release of sFlt-1 from normal placental explants and from preeclamptic placental ex-plants. Preincubation of human umbilical vein endothelial cells or HTR-8/SVneo cells with resveratrol abrogated sFlt-1 release. Resveratrol prevented the up-regulation of early growth response protein-1 (Egr-1), a transcription factor necessary for induction of the vascular endothelial growth factor receptor-1 gene and caused up-regulation of heme oxygenase- 1, a cytoprotective enzyme found to be dysfunctional in preeclampsia.CONCLUSION: In summary, resveratrol can inhibit sFlt-1 release and up-regulate heme oxygenase-1; thus, may offer therapeutic potential in preeclampsia.