组蛋白修饰变化参与曲古抑菌素A缓解的烟草烟雾暴露所致小鼠子宫损伤过程

Involvement of histone modifications in process of uterine injury alleviated by TSA in female mice induced by cigarette smoke exposure

目的研究组蛋白修饰变化在曲古抑菌素A(trichostatin A,TSA)缓解烟草烟雾(cigarette smoke,CS)暴露所致的雌性小鼠子宫损伤过程中的作用。方法通过CS暴露30 d方法制备CS暴露小鼠子宫损伤模型,CS暴露的同时给予TSA进行治疗;HE染色观察各组小鼠子宫组织形态学变化;Western blot技术检测各组小鼠子宫组织H3K4me1、H3K4me2、H3K4me3、H3K9me1、H3K9me2、H3K9me3和H3K27me3总的修饰水平变化以及GLP(euchromatic histone lysine methyltransferase 1,H3K9甲基转移酶),G9ɑ(euchromatic histone lysine methyltransferase 2,H3K9甲基转移酶),EZH2(enhancer of zeste homolog 2,H3K27me3甲基转移酶)的表达水平。结果TSA缓解CS暴露所致的雌性小鼠子宫间质细胞和腺体数量减少等结构改变。TSA有效抑制了CS暴露激活的小鼠子宫组织H3K9me1的表达,但却进一步激活CS暴露诱导的总H3K27me3修饰水平。TSA可以抑制CS暴露激活的小鼠子宫组织GLP和G9ɑ的表达,进一步激活CS暴露诱导的EZH2表达水平。结论组蛋白修饰变化参与CS暴露所致的小鼠子宫损伤以及TSA的缓解损伤过程。

Aim To explore whether histone modifications are involved in the process of uterine injury alleviated by TSA in female mice induced by cigarette smoke(CS)exposure.Methods Female mice were exposed to CS twice daily for 30 days and TSA was injected intraperitoneally into CS-exposed mice on alternate days in the TSA-treated group.HE staining was used to observe the morphological changes of mice uterus after CS exposure;Western blot was used to assess the global modification levels of H3K4me1,H3K4me2,H3K4me3,H3K9me1,H3K9me2,H3K9me3 and H3K27me3 in uteri.GLP(H3K9 histone methyltransferase),G9ɑ(H3K9 histone methyltransferase),EZH2(H3K27me3 histone methyltransferase).Results TSA effectively restored the number of glandular and interstitial cells reduced by CS exposure.Western blot results showed that TSA significantly inhibited global H3K9me1 modification and further aggravated H3K27me3 change induced by CS exposure.Furthermore TSA suppressed GLP and G9ɑexpression in mouse uterine tissue induced by CS exposure,but further activated EZH2 increase.Conclusions Histone modifications are involved in the process of uterine injury alleviated by TSA in female mice induced by cigarette smoke exposure.