目的:研究血管内皮生长因子(VEGF)对子宫中基因表达水平及信号通路的调控作用。方法:利用四环素可逆调节VEGF基因表达的转基因小鼠,通过新一代测序数字基因表达谱(DGE)方法分析在VEGF表达被抑制情况下的子宫基因表达水平。采用实时定量PCR验证部分表达异常的基因。结果:检测到在小鼠子宫中表达的基因约6×106个。其中在VEGF基因表达被抑制条件下,表达水平变化比较明显的基因有2 398个,其中上调的基因为1 231个,主要包括调节细胞内激酶基因、细胞分裂的基因、蛋白折叠的基因等;下调的基因为1 167个,主要包括调节肌肉发育的基因、细胞内基质形成的基因、血管形成的基因等。荧光定量PCR验证表明,基因表达水平变化与转录谱结果高度相关,VEGF抑制后小鼠子宫内表达上调的基因有P2ry14、Eln、Rnf187、Oxtr、Inhbb、Pabpn1、Car2和Mif1(r=0.972),表达下调的基因VEGF、Acta2、Pcx、Tnc、Igfbp3、Cnn1和Hopx(r=0.931)。结论:VEGF表达水平与子宫功能的维持密切相关,为不明原因不孕的诊治提供了新思路。 Objective: To study the regulation of vascular endothelial growth factor (VEGF) on gene expression and signaling pathway in uterus. Methods: The transgenic mice that reversibly regulate the expression of VEGF gene by tetracycline were used to analyze the gene expression of uterus under the inhibition of VEGF expression by a new generation of sequencing digital gene expression profile (DGE). Real-time quantitative PCR was used to verify the partial abnormal expression of genes. Results: About 6 × 106 genes expressed in mouse uterus were detected. Among them, there were 2 398 genes with significant changes in expression levels under the inhibition of VEGF gene expression, of which 1 231 genes were up-regulated, including the regulation of intracellular kinase genes, cell division genes and protein folding genes; The number of down-regulated genes is 1,167, mainly including genes that regulate muscle development, genes formed by intracellular matrix, genes that form blood vessels, and the like. The results of real-time quantitative PCR showed that the gene expression level was highly correlated with the transcriptional result. The expression of genes P2ry14, Eln, Rnf187, Oxtr, Inhbb, Pabpn1, Car2 and Mif1 The down-regulated genes VEGF, Acta2, Pcx, Tnc, Igfbp3, Cnn1 and Hopx (r = 0.931). Conclusion: The expression of VEGF is closely related to the maintenance of uterine function, providing a new idea for the diagnosis and treatment of unexplained infertility.