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Objective  The aim of this study was to investigate the effects of docosahexaenoic acid (DHA) on the generation of angiopoietin-2 (Ang-2) by rat brain microvascular endothelial cells under an oxygen- and glucose-deprivation environment (OGD), and its relationship, if any, with cyclooxygenase 2 (COX-2) expression.    Methods  Annexin V and propidium iodide apoptosis assay was used to detect apoptosis. Enzyme linked immunosorbent assay was used to detect Ang-2, vascular endothelial growth factor (VEGF), prostaglandin E2 (PGE2), and prostaglandin I2 (PGI2) content. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect Ang-2 and VEGF mRNA expression. Western blot was used to detect expression of COX-2 protein.    Results  DHA reduced the apoptosis rate ( P  = 0.026) and decreased the secretion of Ang-2, VEGF, PGE2, and PGI2 ( P  = 0.006,  P  = 0.000,  P  = 0.002,  P  = 0.004 respectively). The relative expression of  Ang2  and  Vegf  mRNA, as well as COX-2 expression, also decreased ( P  = 0.000,  P  = 0.005,  P  = 0.007 respectively). These effects were antagonized by GW9662 (peroxisome proliferator-activated receptor-γ antagonist). COX-2 protein expression levels were positively correlated with  Ang2  and  Vegf  mRNA expression levels (γ = 0.69,  P  = 0.038 and γ = 0.76,  P  = 0.032, respectively).  Ang - 2  and  VEGF  mRNA levels were positively correlated with Ang-2 (γ = 0.84,  P  = 0.012) and VEGF (γ = 0.71,  P  = 0.036) secretion levels respectively.    Conclusion  DHA reduced apoptosis induced by an OGD environment, thus decreasing Ang-2 and VEGF synthesis. This phenomenon was associated with a decrease in COX-2 protein expression, PGE2 and PGI2 secretion, and generation regulation via intracellular transcriptional pathways.

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Effects and mechanisms of docosahexaenoic acid on the generation of angiopoietin-2 by rat brain microvascular endothelial cells under an oxygen- and glucose-deprivation environment