甲基化转移酶抑制剂BIX01294促进小鼠子宫基质细胞迁移、抑制基质细胞蜕膜化  

Methyltransferase inhibitor BIX01294 promotes the migration and inhibits decidualization of mouse uterine stromal cells in vitro

作　　者：廖晖淇 田鎏 杨慧[1,2] 马妮[1,2] 张昌军[1,2,3] 刁红录[1,2,3] 

机构地区：[1]湖北医药学院附属人民医院生殖医学中心,湖北十堰442000 [2]湖北医药学院生物医学工程学院,湖北十堰442000 [3]湖北医药学院胚胎干细胞湖北省重点实验室,湖北十堰442000

出　　处：《南方医科大学学报》2017年第6期730-736,共7页Journal of Southern Medical University

基　　金：国家自然科学基金(31671565);湖北省自然科学基金(2015CFB543);湖北医药学院创新团队(2014CXX03;FDFR201604);湖北医药学院重点学科建设项目资助项目~~

摘　　要：目的探讨甲基化转移酶抑制剂BIX01294(BIX)对小鼠子宫内膜基质细胞迁移和蜕膜化过程的作用和影响。方法取妊娠第3.5天小鼠子宫分离培养得小鼠子宫内膜基质细胞,采用细胞划痕运动分析、体外诱导小鼠子宫内膜基质细胞蜕膜化模型及Real-time PCR方法分别从形态学和分子生物学角度观察BIX对小鼠子宫内膜基质细胞迁移及蜕膜化的影响。结果在一定浓度范围内(BIX≤15μmol/L),小鼠子宫内膜基质细胞的迁移距离随着BIX浓度的升高而增加,与对照组相比,BIX 15μmol/L处理组基质细胞的迁移距离增加最明显,差异具有统计学意义,当BIX浓度提高到20μmol/L时,细胞迁移距离增加不明显,且此时开始出现细胞的死亡;与对照组相比,BIX处理24 h组小鼠子宫内膜基质细胞Ehmt2 m RNA表达显著下调(P<0.01);并且15μmol/L BIX能够抑制小鼠子宫内膜基质细胞蜕膜化反应。结论一定浓度范围的BIX通过抑制Ehmt2m RNA在基质细胞中的表达促进小鼠子宫内膜基质细胞的迁移,并且对小鼠子宫基质细胞的蜕膜化过程有抑制作用。Objective To investigate the effect of BIX01294 （BIX）, a methyltransferase inhibitor, on the migration and decidualization of the stromal cells in mouse uterus. Methods Mouse endometrial stromal cells were isolated and cultured from the uterus of pregnant mice on day 3.5 of gestation. The migration and decidualization of mouse endometrial stromal cells treated with BIX at different concentrations were observed with wound healing assay and real-time PCR. Results The migration distance of mouse endometrial stromal cells increased as the BIX concentration increased within the range below 15 μmol/L. Compared with the control cells, the cells treated with BIX （15 μmol/L） showed significantly increased migration distances, but increasing BIX concentration to 20 μmol/L did not further increase the cell migration distance and began to cause cell death. Compared with the control cells, the BIX-treated stromal cells exhibited significantly down-regulated expression of Ehmt2 mRNA, and 15 μmol/L BIX caused inhibition of decidualization in the stromal cells. Conclusion Within a defined concentration range, BIX promotes the migration and inhibits decidualization of mouse uterine stromal cells by inhibiting the expression of Ehmt2 mRNA.

关 键 词：子宫内膜基质细胞 迁移 蜕膜化 BIX01294 组蛋白甲基化 

分 类 号：R714[医药卫生—妇产科学]