砷染毒对家兔皮肤雌激素受体α、β和PI3K mRNA表达的影响及性别差异  

Effects of arsenic exposure on expressions of ERα, ERβ, and PI3K mRNA in rabbit skin and sex difference

作　　者：古丽达娜·塔布斯别克 马瑶 白雪 涂开荣 吴军 Gulidana TABUSIBIEKE;MA Yao;BAI Xue;TU Kai-rong;WU Jun(Department of Occupational and Environmental Health,School of Public Health,Xinjiang Medical University,Urumqi,Xinjiang 830011,China)

机构地区：[1]新疆医科大学公共卫生学院劳动卫生与环境卫生学教研室,新疆乌鲁木齐830011

出　　处：《环境与职业医学》2020年第3期254-259,共6页Journal of Environmental and Occupational Medicine

基　　金：新疆维吾尔自治区自然科学基金项目(2018D01C147)。

摘　　要：[背景]砷作为一种环境内分泌干扰物,能够发挥雌激素样效应,其对皮肤雌激素效应靶基因的毒作用机制尚未完全阐明。[目的]观察砷暴露以及DNA甲基化抑制剂5-氮杂-2’-脱氧胞苷(5-Aza-dc)干预砷暴露对不同性别家兔皮肤组织中雌激素受体α(ERα)、雌激素受体β(ERβ)和磷脂酰肌醇-3激酶(PI3K)mRNA表达的影响,并探讨其在砷的皮肤毒作用性别差异中的作用。[方法]将家兔分为:空白对照组、低剂量砷组(0.075 mg·kg^-1·周-1)、中剂量砷组(0.15 mg·kg^-1·周-1)、高剂量砷组(0.75 mg·kg^-1·周-1)、5-Aza-dc干预低剂量砷组、5-Aza-dc干预中剂量砷组、5-Aza-dc干预高剂量砷组7组,每组8只,雌雄各半。家兔自由饮水,持续染毒14周,自第9周开始,5-Aza-dc干预组家兔经耳缘静脉注射0.125 mg·kg^-15-Aza-dc,每周2次,连续注射6周。第14周末对每组家兔背部同一部位采用皮肤活检术剖取全部皮肤。通过实时荧光定量PCR(RT-PCR)法检测不同性别家兔皮肤组织中ERα、ERβ和PI3K mRNA表达水平。[结果]家兔皮肤组织中,雌性低、高剂量砷组ERαmRNA(分别为1.67±0.10和2.95±0.38)较对照组表达升高(P<0.05),雄性高剂量砷组ERαmRNA(2.88±0.43)较对照组表达升高(P<0.05)。雄性低、高剂量砷组ERβmRNA(分别为0.75±0.02和0.59±0.29)较对照组降低(P<0.05);低、高剂量砷组ERβmRNA表达量雄性低于雌性(雌性分别为0.90±0.08和1.48±0.58)(P<0.05)。雄性低剂量砷组PI3K mRNA表达量低于雌性(分别为0.70±0.22和1.40±0.10)(P<0.05);雄性5-Aza-dc干预各剂量砷组ERβ和PI3K mRNA与对照组相比,均明显降低(均P<0.05)。[结论]砷暴露可诱导雌雄家兔皮肤组织中ERαmRNA表达升高,雄性家兔皮肤组织ERβm RNA和PI3K mRNA表达降低,且均为雌性高于雄性。砷诱导的ERα、ERβ和PI3K mRNA表达的性别差异可能在砷毒作用差异中发挥作用;5-Aza-dc可能会加剧雌雄间差异。[Background] Arsenic(As) acts as an environmental endocrine disruptor to exert estrogen-like effects, and its toxic mechanism on target genes of estrogen effect in skin has not been fully elucidated. [Objective] This experiment is designed to observe the effects of arsenic exposure and the intervention of 5-Aza-2’-deoxycytidine(5-Aza-dc, an DNA methylation inhibitor) on the expressions of estrogen receptor α(ERα), estrogen receptor β(ERβ) and phosphoinositide 3-kinase(PI3K) m RNA in the skin tissues of rabbits of different sexes, and to explore the roles of estrogen effect target gene m RNA expressions in the sex difference of arsenic skin toxicity. [Methods] Rabbits were randomly divided into seven groups: blank control group, low-dose arsenic group(0.075 mg·kg^-1·week-1), medium-dose arsenic group(0.15 mg·kg^-1·week-1), high-dose arsenic group(0.75 mg·kg^-1·week-1), 5-Aza-dc intervention against low-dose arsenic group, 5-Aza-dc intervention against medium-dose arsenic group, and 5-Aza-dc intervention against high-dose arsenic group, with eight animals in each group, half male and half female. The rabbits were given free drinking water and continuously administered the corresponding arsenic dosages for 14 weeks. From the 9 th week, the 5-Aza-dc intervention groups received intravenous injection of 0.125 mg·kg^-1 5-Aza-dc through ear vein twice a week for six weeks. At the end of the 14 th week, biopsy of full-thickness skin was performed on the same region on the back of each rabbit. The expression levels of ERα, ERβ and PI3K m RNA in skin tissues of rabbits of different sexes were detected by real-time fluorescence quantitative PCR(RT-PCR). [Results] In the rabbit skin tissues, the expression levels of ERα m RNA in the female low-and high-dose arsenic groups(1.67±0.10 and 2.95±0.38, respectively) and in the male high-dose arsenic group(2.88±0.43) were higher than that in the control group(P < 0.05). The expression levels of ERβ m RNA in the male low-and high-dose arsenic groups(0.75±0.02 an

关 键 词：砷 5-氮杂-2’-脱氧胞苷 雌激素受体 PI3K 皮肤 家兔 

分 类 号：R114[医药卫生—卫生毒理学]