高糖对大鼠微血管内皮细胞基因表达谱的影响

Influence of high glucose concentration milieu on gene expression spectrum of rat pulmonary microvascular endothelial cell

目的 研究高糖对SD大鼠肺微血管内皮细胞基因表达谱的影响 ,进一步探索高糖导致微血管内皮细胞功能紊乱的可能分子机制。方法 体外培养SD大鼠肺微血管内皮细胞 ,以Affymetrix公司的RG- U34A基因芯片分别检测正常浓度 (5 .5 6mmol/L)和高浓度 (2 0mmol/L)D- 葡萄糖培养基中培养 2 4h后内皮细胞的基因表达谱。结果 高糖培养细胞较正常浓度糖培养细胞有 96 1个基因表达下调 ,5 0 9个基因表达上调 ,其中变化幅度大于 2倍的分别有 2 2个 (P >0 .998)和 11个 (P <0 .0 0 2 5 ) ,这些基因主要与细胞物质代谢、细胞信息传递、细胞膜结构、细胞外基质合成及分解等有关。结论 高糖可能通过影响微血管内皮物质代谢、信号转导、细胞膜结构和细胞外基质等的表达而导致血管内皮功能紊乱。

Objective To observe the gene expression spectrum of pulmonary microvascular endothelial cells of SD rat in high glucose concentration culture media and to investigate further the possible genes of microvascular endothelial cell which may be involved in the detrimental effect of high glucose resulting in microvascular endothelial dysfunction.Methods Pulmonary Microvascular endothelial cells of SD rat were cultured in 5.56 mmol/L glucose(NG) and 20 mmol/L glucose(HG) media respectively for 24 h, and then RG-U34A gene chips from Affymetrix Corporation were applied to test the gene expression of endothelial cells in the two groups. Results Comparing with gene expression in NG group, the HG group had 33 genes expression which was 2 folds greater, including down-regulation of 22 genes (Wilcoxon signed rank test, P> 0.998) and up-regulation of 9 genes (Wilcoxon signed rank test, P< 0.0025). The functions of these genes mainly covered the cellular metabolism, structural components of extracellular matrix (ECM), and signal transduction. Conclusion High glucose concentration can influence the ECM genes regulating metabolism, signal transduction and protein synthesis in the microvascular endothelial cells which lead to endothelial dysfunction.