H202在大鼠胚胎发育中对NSD1基因表达及组蛋白甲基化的影响

来源 :中华医学会2012年医学遗传学年会暨全国第十一次医学遗传学学术会议 | 被引量 : 0次 | 上传用户:sjzshiyijshan
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  目的 氧化应激是指机体在遭受各种有害刺激时,体内活性分子如活性氧自由基(reactive oxygen species,ROS)和活性氮自由基(reactive nitrogen species,RNS)产生过多,氧化程度超出氧化物的清除,从而导致组织损伤;已有研究显示氧化应激能够干扰胚胎的发育,引起多种出生缺陷的发生.然而,组蛋白的甲基化是否是受氧化应激影响而导致出生缺陷尚不清楚.Nuclear receptor-binding SET domain protein1(NSD1)是一种重要的甲基转移酶,能够催化组蛋白H3第36位赖氨酸(H3K36)的甲基化,本研究以H2O2为氧化应激诱导因素,拟探索其在大鼠胚胎发育过程中对胚胎发育的影响、引发的氧化应激反应以及对组蛋白甲基化的作用.方法 通过腹腔注射的方法给予SD孕大鼠H2O2刺激,观察胚胎的表型变化,鉴定大鼠胚胎各组织器官的氧化应激反应、NSD1基因表达水平及组蛋白甲基化的变化.结果 给予H2O2刺激后大鼠胚胎平均的身长、体重都有下降的趋势(p<0.05);心脏、肾脏、大脑以及胃肠组织的总抗氧化能力发生代偿性升高;NSD1 mRNA表达在各组织中均下降,且H3K36me3的水平在各器官中都有下降趋势.结论 H2O2诱导的氧化应激反应可能引起大鼠胚胎发育迟缓,并且能够使胚胎多种器官NSD1基因的表达下降,引起H3K36me3的水平下降.
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