杨德山, 洪峰. 氟、砷染毒对大鼠破骨细胞骨吸收能力的影响及其机制[J]. 环境与职业医学, 2018, 35(4): 297-302. DOI: 10.13213/j.cnki.jeom.2018.17694
引用本文: 杨德山, 洪峰. 氟、砷染毒对大鼠破骨细胞骨吸收能力的影响及其机制[J]. 环境与职业医学, 2018, 35(4): 297-302. DOI: 10.13213/j.cnki.jeom.2018.17694
YANG De-shan, HONG Feng. Effects of fluoride and arsenic exposure on bone absorptive capacity of osteoclasts in rats and related mechanism[J]. Journal of Environmental and Occupational Medicine, 2018, 35(4): 297-302. DOI: 10.13213/j.cnki.jeom.2018.17694
Citation: YANG De-shan, HONG Feng. Effects of fluoride and arsenic exposure on bone absorptive capacity of osteoclasts in rats and related mechanism[J]. Journal of Environmental and Occupational Medicine, 2018, 35(4): 297-302. DOI: 10.13213/j.cnki.jeom.2018.17694

氟、砷染毒对大鼠破骨细胞骨吸收能力的影响及其机制

Effects of fluoride and arsenic exposure on bone absorptive capacity of osteoclasts in rats and related mechanism

  • 摘要: 目的 研究氟砷联合染毒对大鼠破骨细胞骨吸收能力的影响及其机制。

    方法 54只清洁级SD大鼠随机分为9组,每组6只,雌雄各半。根据预实验及文献确定染毒剂量,用NaF和NaAsO2分别对实验动物予以灌胃染毒,各染毒组毒物剂量及缩写分别为:对照组(F0As0)、低氟组(5 mg/kg,F5)、高氟组(20 mg/kg,F20)、低砷组(2.5 mg/kg,As2.5)、高砷组(10 mg/kg,As10)、低氟低砷组(5 mg/kg+2.5 mg/kg,F5As2.5)、低氟高砷组(5 mg/kg+10 mg/kg,F5As10)、高氟低砷组(20 mg/kg+2.5 mg/kg,F20As2.5)、高氟高砷组(20 mg/kg+10 mg/kg,F20As10)。酶联免疫吸附法(ELISA法)测定大鼠血清中抗酒石酸酸性磷酸酶5b(TRACP-5b)、Ⅰ型胶原吡啶交联终肽(ICTP)含量及大鼠右侧股骨组织匀浆上清液中骨保护素(OPG)、前列腺素E2(PGE2)、1,25二羟基维生素D31,25(OH)2D3含量。

    结果 大鼠血清中ICTP、TRACP-5b蛋白表达水平在高氟组均较对照组升高(F0As0:1.352±0.025,2.942±0.078;F20:1.427±0.026,3.202±0.142;均P < 0.05),而单独染砷组与对照组的差异均无统计学意义(Ps>0.05)。对于氟砷联合染毒组,染氟剂量在20mg/kg时,ICTP、TRACP-5b蛋白含量在高氟高砷组较高氟低砷组明显降低(F20As2.5:1.442±0.034,3.280±0.095;F20As10:1.345±0.042,3.053±0.084;均P < 0.05)。氟砷的偏相关分析及交互作用结果显示TRACP-5b、ICTP蛋白含量的改变与氟浓度呈正相关(偏相关系数:0.663,0.392;均P < 0.05),氟起到主效应作用(F=24.560,8.188;均P < 0.05)。大鼠骨组织OPG、PGE2、1,25(OH)2D3表达水平在高氟组均较对照组升高(F0As0:12.278±0.220,1.352±0.025,9.582±0.363;F20:14.087±0.797,1.427±0.026,11.915±0.931;均P < 0.05)。对于氟砷联合染毒组,染氟剂量为2.5 mg/kg时,低氟高砷组的PGE2较低氟低砷组低(F5As2.5:1.442±0.034;F5As10:1.345±0.080;P < 0.05);染氟剂量为20 mg/kg时,高氟高砷组1,25(OH)2D3较高氟低砷组低(F20As2.5:12.082±0.860;F20As10:10.567±0.695;均P < 0.05)。氟砷的偏相关分析及交互作用结果显示OPG、PGE2、1,25(OH)2D3含量改变与氟呈正相关(偏相关系数:0.804,0.487,0.748;均P < 0.05),氟起到主效应作用(F=47.100,9.031,3.114;均P < 0.05);砷对OPG、PGE2、1,25(OH)2D3的直接影响不明显(P>0.05)。

    结论 砷能抑制氟暴露对大鼠破骨细胞骨吸收功能的促进作用,氟砷之间的交互作用主要表现为拮抗作用。PGE2、1,25(OH)2D3可能是氟砷对破骨细胞骨吸收功能进行调控的重要因子。

     

    Abstract: Objective To explore the toxicity and mechanism of combined exposure to fluoride and arsenic on bone absorptive capacity of osteoclasts in rats.

    Methods A total of 54 SD rats of clean grade were randomly divided into 9 groups, with 6 rats in each group (half males and half females). Based on a pilot experiment and literature review, the animals were treated with NaF and NaAsO2 by intragastric administration:control group (F0As0), low fluoride group (5mg/kg, F5), high fluoride group (20mg/kg, F20), low arsenic group (2.5mg/kg, As2.5), high arsenic group (10 mg/kg, As10), low fluoride and low arsenic group (5 mg/kg+2.5 mg/kg, F5As2.5), low fluoride and high arsenic group (5 mg/kg+10 mg/kg, F5As10), high fluoride and low arsenic group (20 mg/kg+2.5 mg/kg, F20As2.5), and high fluoride and high arsenic group (20 mg/kg+10 mg/kg, F20As10). The levels of tartrateresistant acid phosphatase 5b (TRACP-5b) and pyridinoline cross linked carboxyterminal telopeptide of type Ⅰ collagen (ICTP) in rat serum, as well as the levels of osteoprotegerin (OPG), prostaglandin (PGE2), and 1, 25-dihydroxy vitamin D31, 25(OH)2D3 in homogenate supernatant of right femur tissue samples were determined by ELISA.

    Results The expression levels of ICTP and TRACP-5b in the high fluoride group were higher than those in the control group (F0As0:1.352±0.025, 2.942±0.078; F20:1.427±0.026, 3.202±0.142; Ps < 0.05), while there was no significant difference between any individual arsenic exposure group and the control group (Ps>0.05). The expression levels of ICTP and TRACP-5b in the high fluoride and high arsenic group were lower than those in the high fluoride and low arsenic group (F20As2.5:1.442±0.034, 3.280±0.095; F20As10:1.345±0.042, 3.053±0.084; Ps < 0.05). The results of partial correlation analysis and interaction analysis showed that the expression levels of TRACP-5b and ICTP were positively correlated with fluoride concentration (partial correlation coefficient:0.663, 0.392; Ps < 0.05), and fluoride showed the main effect (F=24.560, 8.188; Ps < 0.05). The expression levels of OPG, PGE2, and 1, 25(OH)2D3 in the groups treated with high doses of fluoride were significantly higher than those in the control group (F0As0:12.278±0.220, 1.352±0.025, 9.582±0.363; F20:14.087±0.797, 1.427±0.026, 11.915±0.931; Ps < 0.05). The expression level of PGE2 in the low fluoride and high arsenic group was lower than that in the low fluoride and low arsenic group (F5As2.5:1.442±0.034; F5As10:1.345±0.080; P < 0.05). The expression level of 1, 25(OH)2D3 in the high fluoride and high arsenic group was lower than that in the high fluoride and low arsenic group (F20As2.5:12.082±0.860; F20As10:10.567±0.695; Ps < 0.05). The results of partial correlation analysis and interaction analysis showed that the expression levels of OPG, PGE2, and 1, 25(OH)2D3 were positively correlated with fluoride concentration (partial correlation coefficient:0.804, 0.487, 0.748; Ps < 0.05), and fluoride showed as the main effect (F=47.100, 9.031, 3.114; Ps < 0.05); the direct toxic effects of arsenic on OPG, PGE2, and 1, 25(OH)2D3 were minor (P>0.05).

    Conclusion Arsenic can inhibit the auxo-action of fluorine on the bone absorption of osteoclasts in rats, and the fluorine-arsenic interaction is mainly antagonistic. PGE2 and 1, 25(OH)2D3 may be important factors in the regulation of osteoclast bone absorption function.

     

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