覃子秀, 杨兴, 王冰洁, 张涛, 黄一铭, 张均涛, 金照凤, 洪峰. 氟砷联合染毒对大鼠牙齿组织BMP-2RANKPI3KAkt1基因转录水平的影响[J]. 环境与职业医学, 2018, 35(8): 702-708. DOI: 10.13213/j.cnki.jeom.2018.18228
引用本文: 覃子秀, 杨兴, 王冰洁, 张涛, 黄一铭, 张均涛, 金照凤, 洪峰. 氟砷联合染毒对大鼠牙齿组织BMP-2RANKPI3KAkt1基因转录水平的影响[J]. 环境与职业医学, 2018, 35(8): 702-708. DOI: 10.13213/j.cnki.jeom.2018.18228
QIN Zi-xiu, YANG Xing, WANG Bing-jie, ZHANG Tao, HUANG Yiming, ZHANG Jun-tao, JIN Zhao-feng, HONG Feng. Effects of co-exposure to fluoride and arsenic on mRNA expressions of BMP-2, RANK, PI3K, and Akt1 in dental tissues of rats[J]. Journal of Environmental and Occupational Medicine, 2018, 35(8): 702-708. DOI: 10.13213/j.cnki.jeom.2018.18228
Citation: QIN Zi-xiu, YANG Xing, WANG Bing-jie, ZHANG Tao, HUANG Yiming, ZHANG Jun-tao, JIN Zhao-feng, HONG Feng. Effects of co-exposure to fluoride and arsenic on mRNA expressions of BMP-2, RANK, PI3K, and Akt1 in dental tissues of rats[J]. Journal of Environmental and Occupational Medicine, 2018, 35(8): 702-708. DOI: 10.13213/j.cnki.jeom.2018.18228

氟砷联合染毒对大鼠牙齿组织BMP-2RANKPI3KAkt1基因转录水平的影响

Effects of co-exposure to fluoride and arsenic on mRNA expressions of BMP-2, RANK, PI3K, and Akt1 in dental tissues of rats

  • 摘要: 目的 通过建立慢性氟砷联合染毒大鼠模型,观察骨形态发生蛋白2(BMP-2)、核因子κB受体活化因子(RANK)、磷脂酰肌醇-3激酶(PI3K)、蛋白激酶B1(Akt1)基因mRNA相对表达水平在氟砷联合染毒大鼠牙齿组织中的变化情况。

    方法 选取清洁级Wistar大鼠作为研究对象,按析因设计随机分为16组,每组10只,雌雄各半,采用不同浓度NaF(0.0、5.0、10.0、20.0 mg/kg)和NaAsO2(0.0、2.5、5.0、10.0 mg/kg)单独和联合灌胃染毒,每周连续灌胃染毒6 d,停灌1 d,连续染毒6个月。实验结束后处死大鼠。采用氟离子选择电极测牙氟含量,原子荧光光谱法测牙砷含量,实时荧光定量PCR检测大鼠牙齿组织BMP-2RANKPI3KAkt1 mRNA相对量表达。

    结果 无氟染毒的4组大鼠均无氟斑牙发生,余12组大鼠均出现氟斑牙。牙氟、牙砷含量随单独氟、砷染毒剂量升高而增加。大鼠牙齿组织BMP-2Akt1 mRNA表达水平呈现随氟染毒剂量增加而升高的趋势(P<0.05),但并未随砷染毒剂量的改变而发生变化(P>0.05)。RANKPI3K mRNA表达水平呈现随氟染毒剂量增加而下降的趋势(P<0.05),各砷染毒剂量组间差异则无统计学意义(P>0.05)。氟染毒剂量、牙氟含量与BMP-2Akt1 mRNA表达水平呈正相关(r=0.382、0.302,0.292、0.246,均P<0.05),与RANKPI3K mRNA表达水平呈负相关(r=-0.323、-0.332,-0.193、-0.185,均P<0.05),氟斑牙与牙齿组织RANKPI3K mRNA表达呈负相关(r=-0.283、-0.273,均P<0.05),其余无相关性。

    结论 过量氟暴露可上调大鼠牙组织BMP-2Akt1转录水平,下调RANKPI3K转录水平,从而参与牙齿釉质发育或矿化过程,导致牙齿损伤。氟砷联合暴露致牙齿损伤主要表现为氟的主效应,砷间接参与氟致牙齿损伤作用。

     

    Abstract: Objective To observe changes in mRNA expressions of bone morphogenetic protein Ⅱ (BMP-2), receptor activator of nuclear factor kappa-B (RANK), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt1) in dental tissues of the rats with chronic coexposure to arsenic and fluoride.

    Methods Clean Wistar rats were divided randomly into 16 groups by factorial design, with 10 rats in each group (half female and half male), and intragastrically exposed to different doses of NaF (0.0, 5.0, 10.0, and 20.0 mg/kg), NaAsO2 (0.0, 2.5, 5.0, and 10.0 mg/kg), or the combination of NaF and NaAsO2 for 6 days per week and continuously 6 months. The levels of teeth fluoride (TF) and teeth arsenic (TAs) were determined by fluoride ion selective electrode method and atomic fluorescence spetrometry. The mRNA expressions of BMP-2, RANK, PI3K, and Akt1 were detected by quantitative real-time PCR.

    Results There was no dental fluorosis found in the four groups without fluoride exposure, but in the other 12 groups with fluoride exposure. TF and TAs levels increased with higher independent fluoride or arsenic exposure doses. The mRNA expression levels of BMP-2 and Akt1 in dental tissues of rats increased with higher fluoride exposure doses (P<0.05), but not changed with higher arsenic exposure doses (P>0.05). The mRNA expression levels of RANK and PI3K in dental tissues of rats decreased with higher fluoride exposure doses (P<0.05), but did not change with higher arsenic exposure doses (P>0.05). Fluoride exposure doses and dental fluoride levels were positively associated with the mRNA expression of BMP-2 or Akt1 (r=0.382, 0.302, 0.292, or 0.246, Ps<0.05), but negatively associated with the mRNA expression of RANK or PI3K (r=-0.323, -0.332, -0.193, -0.185, Ps<0.05). Dental fluorosis was negatively associated with the mRNA expression of RANK or PI3K (r=-0.283 or -0.273, Ps<0.05). No association was found between other indicators.

    Conclusion Exposure to excessive fluoride can affect teeth enamel development or mineralization and induce dental injury by up-regulating the transcription level of BMP-2 and Akt1 and reducing the transcription level of RANK and PI3K in rat dental tissues. Fluoride plays a key role in dental fluorosis caused by joint exposure to fluoride and arsenic, and arsenic is indirectly involved in developing dental fluorosis.

     

/

返回文章
返回