Bcl2相互作用蛋白3在子宫内膜组织中的表达及其在子宫内膜异位症发病中的意义

The significance of BNIP3 in the pathogenesis of endometriosis analyzing through the methods of molecular biology and bioinformatics

目的探究Bcl2相互作用蛋白3(BCL2 Interacting Protein 3,BNIP3)表达变化与正常子宫内膜周期的关系及在子宫内膜异位症(EMs)发病中的意义。方法从GEO数据库获得GSE51981、GSE6364、GSE4888、GSE25628的基因表达谱,通过生物信息学手段比较正常子宫内膜周期组增殖期到分泌期基因表达变化,分析基因富集情况以及BNIP3在正常子宫内膜月经周期中的表达变化;比较数据集中正常子宫内膜周期组人群与内异症病人差异趋势表达基因以及各样本中BNIP3的表达,总结其在EMs发病中的意义;取23例Ⅲ⁃ⅣEMs病人正位及异位子宫内膜组织,以及25例因子宫肌瘤行子宫切除术病人的子宫内膜组织作为正常对照,通过实时荧光定量qRT⁃PCR及蛋白质印迹法(Western Blot)检测BNIP3在各组织中的表达,验证BNIP3表达变化同EMs发病的关系。结果GSE4888、GSE6364、GSE51981数据集中,BNIP3在增殖期与分泌期相对表达量分别为100.22±16.54、332.80±32.29,487.68±100.09、1425.83±157.47,8.36±0.69、9.82±0.71,均差异有统计学意义(P<0.0001);GSE25628数据集中,BNIP3在正常子宫内膜组织、EMs病人正位、EMs病人异位子宫内膜组织中的表达量分别为(10.11±0.72)、(9.19±0.56)、(8.52±0.57),三组间对比差异有统计学意义;临床样本中,正常内膜组织、EMs正位内膜组织、EMs异位内膜组织中BNIP3的mRNA表达量分别为1.15±0.57、0.56±0.19、0.36±0.08,三组间对比差异有统计学意义;BNIP3蛋白在正常子宫内膜组织、EMs正位内膜组织、EMs异位内膜组织中的表达水平分别为1.00±0.41、0.58±0.20、0.38±0.12,三组间对比均差异有统计学意义。结论BNIP3在子宫内膜组织中的表达降低与EMs的发生具有相关性。

Objective To explore the relationship between BNIP3 expression and normal endometrial cycle and its significance in the pathogenesis of endometriosis(EMs).Methods Gene expression profiles of GSE51981,GSE6364,GSE4888 and GSE25628 were obtained from the GEO database.First,the changes of gene expression of normal endometrial tissues in the proliferative phase and the secretory phase were compared by bioinformatics method,and the gene enrichment and BNIP3 expression were analyzed.Secondly,the differential expressed genes of normal population and endometriosis patients in the data set and the expression of BNIP3 in each sample were analyzed.Finally,the endometrial tissues of 23 patients withⅣ⁃ⅣEMs and 25 patients who underwent hysterectomy for uterine fibroids were taken as normal controls.The expression of BNIP3 in all tissues was detected by qRT⁃PCR and Western Blot to verify the relationship between BNIP3 expression and the incidence of EMs.Results In the data set of GSE4888,GSE6364 and GSE51981,the relative expressions of BNIP3 in the proliferation and secretion phases were(100.22±16.54)vs.(332.80±32.29),(487.68±100.09)vs.(1425.83±157.47)vs.(8.36±0.69)vs.(9.82±0.71)respectively,and the differ⁃ences were statistically significant(P<0.0001).According to GSE25628 data set,the expression of BNIP3 in in normal endometri⁃al tissues,EMs orthotopic endometrial tissues and EMs ectopic endometrial tissues were(10.11±0.72),(9.19±0.56),and(8.52±0.57),respectively.Among the clinical samples,the mRNA expressions of BNIP3 in normal endometrial tissues,EMs orthotopic en⁃dometrial tissues and EMs ectopic endometrial tissues were 1.15±0.57,0.56±0.19 and 0.36±0.08,respectively.The expression levels of BNIP3 protein in normal endometrial tissues,EMs orthotopic endometrial tissues and EMs ectopic endometrial tissues were 1.00±0.41,0.58±0.20 and 0.38±0.12,respectively.Conclusion The change of BNIP3 expression in endometrial tissue is closely related to the maintenance of normal menstruation,and the decrease of BNIP3 expression is correlated with the occurrence of EMs.