CAJ | 학술논문

目的了解DNA甲基化转移酶(DN MTs)、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(P＜0.05),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.
목적 료해DNA갑기화전이매(DN MTs)、조단백을선화매(HAT)화조단백거을선화매(HDAC)재추병완(BP)대웅성대서고환생식독성중적작용.방법 장27지대서수궤분위3조,1-BP염독조、2-BP염독조화대조조분별급여복강주사1-BP、2-BP、옥미유,련속염독2주,평개정자수량화형태.운용실시정량PCR화매련면역흡부법(ELISA)대갑기화전이매(DNMT1、DNMT3a、DNMT3b)적mRNA표체수평급을선화매화거을선화매적활력진행검측.결과 여대조조비교,BPs적폭로사대서부고정자적절대수량화상대수량감소,1-BP주요사무미정자비례증가,이2-BP폭로사두부이상정자적비례증가.여대조조비교,2-BP적폭로사대서DNMTs적mRNA표체수평하강,차이유통계학의의(P＜0.05)；여대조조상비,1-BP폭로대대서고환적HAT화HDAC활력수평무영향,2-BP폭로사대서고환HAT활력수평승고,차이유통계학의의(P＜0.05),대HDAC활력수평영향무통계학의의.결론 2-추병완적폭로가능유도DNA갑기화화조단백을선화수평적이상,표관유전조공가능재2-추병완생식독성과정중기중요작용.
Objective To investigate the changes in the expression of DNA methyltransferases (DNMTs)and activities of histone acetyltransferase (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.