溴丙烷对雄性大鼠睾丸组织DNA甲基化酶及组蛋白乙酰化水平的影响  

Effects of bromopropane exposure on expression of DNA methyltransferases and level of histone acetylation in testis of male rats

作　　者：张茜[1] 郑睿智[1] 张志华[1] 杨林胜[1] 王华[2] 宁萑[2] 黄芬[1] 

机构地区：[1]安徽医科大学公共卫生学院流行病与卫生统计学系,合肥230032 [2]安徽医科大学公共卫生学院流行病与卫生毒理学系,合肥230032

出　　处：《中华劳动卫生职业病杂志》2013年第2期92-95,共4页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金资助项目（30700656）,安徽医科大学博士科研资助项目（XJ200908）

摘　　要：目的了解DNA甲基化转移酶（DNMTs）、组蛋白乙酰化酶（HAT）和组蛋白去乙酰化酶（HDAC）在溴丙烷（BP）对雄性大鼠睾丸生殖毒性中的作用。方法将27只大鼠随机分为3组，1-BP染毒组、2-BP染毒组和对照组分别给予腹腔注射1-BP、2-BP、玉米油，连续染毒2周，评价精子数量和形态。运用实时定量PCR和酶联免疫吸附法（ELISA）对甲基化转移酶（DNMT1、DNMT3a、DNMT3b）的mRNA表达水平及乙酰化酶和去乙酰化酶的活力进行检测。结果与对照组比较，BPs的暴露使大鼠附睾精子的绝对数量和相对数量减少，1-BP主要使无尾精子比例增加，而2-BP暴露使头部异常精子的比例增加。与对照组比较，2-BP的暴露使大鼠DNMTs的mRNA表达水平下降，差异有统计学意义（P〈0．05）；与对照组相比，1-BP暴露对大鼠睾丸的HAT和HDAC活力水平无影响，2-BP暴露使大鼠睾丸HAT活力水平升高，差异有统计学意义（P0．05），对HDAC活力水平影响无统计学意义。结论2-溴丙烷的暴露可能诱导DNA甲基化和组蛋白乙酰化水平的异常，表观遗传调控可能在2-溴丙烷生殖毒性过程中起重要作用。Objective To investigate the changes in the expression ofDNA methyltransferases （DNMTs） and activities of histone aeetyhransferase （HAT） and histone deacetylase （HDAC） in the testis of male rats exposed to bromopropanes （BPs）. Methods Twenty-seven male rats were randomly divided into three groups to be intraperitoneally injected with 1-BP, 2-BP, or corn oil （as a control） for two weeks. The sperm count and morphology in the epididymis were evaluated. The mRNA expression of DNMT1, DNMT3a, and DNMT3b and activities of HAT and HDAC in the testis were measured by quantitative real-time PCR and ELISA. Results Compared with the control group, the BP exposure groups showed significant decreased absolute and relative sperm counts; the proportion of tailless sperm increased in the 1-BP exposure group, while the proportion of sperm with abnormal heads increased in the 2-BP exposure group. The 2-BP exposure group had significantly lower mRNA expression of DNMT1, DNMT3a, and DNMT3b than the control group （P〈0.05）. There were no significant differences in the activities of HAT and HDAC between the control group and 1-BP exposure group; the 2-BP exposure group showed significantly higher HAT activity than the control group （P〈0.05）, but no significant difference was found in HDAC activity between them. Conclusion Exposure to 2-BP might induce abnormal DNA methylation and histone acetylation, and epigenetic regulation might play an important role in the reproductive toxicity of 2-BP.

关 键 词：溴丙烷 生殖毒性 DNA甲基化 组蛋白乙酰化 去乙酰化 

分 类 号：R114[医药卫生—卫生毒理学]