慢性氟砷联合暴露对大鼠骨骼Runx2及其下游相关因子的影响
만성불신연합폭로대대서골격Runx2급기하유상관인자적영향
Chronic combined effects of fluoride and arsenite on the Runx2 and downstream related factors of bone metabolism in rats
  • 万方数据
    中华预防医学杂志 중화예방의학잡지
    CHINESE JOURNAL OF
    2013年 9期 794-798 ,共5页

    洪峰%郑冲%徐德淦%钱亚利

    홍봉%정충%서덕감%전아리

    氟%砷%大鼠%联合作用%Runx2 氟%砷%大鼠%聯閤作用%Runx2
    불%신%대서%연합작용%Runx2
    Fluoride%Arsenite%Rats%Combined effects%Runx2
    目的 研究慢性氟砷联合暴露对大鼠骨骼代谢Runx2及其下游相关因子的影响.方法 将54只8周龄清洁级SD大鼠按析因设计方法随机分成9组,每组6只,雌雄各半,分为对照组、低氟组、高氟组、低砷组、高砷组、低氟低砷组、低氟高砷组、高氟低砷组及高氟高砷组.使用氟化钠(NaF,低氟组5mg/kg、高氟组20 mg/kg)和亚砷酸钠(NaAsO2,低砷组2.5 mg/kg、高砷组10 mg/kg)灌胃染毒6个月；测定大鼠骨骼中Runx2、基质金属蛋白酶9(MMP-9)、成骨相关转录因子(Osterix)核因子-κB受体活化因子配基(RANKL)蛋白浓度.结果 对照组、低砷组、高砷组无氟斑牙出现,低氟组、高氟组氟斑牙比例(分别为5/6、6/6)与对照组(O)相比,差异均有统计学意义(x2=8.57、12.00,p＜0.05).骨氟含量随着氟染毒剂量的增加而升高,无氟染毒组[对照组、低砷组、高砷组的几何均数(最小值～最大值)分别为0.005(0.003 ～0.009)、0.006(0.003～0.021)、0.007(0.002～0.100)mg/g]、低氟组[低氟组、低氟低砷组、低氟高砷组分别为3.395(2.416 ～5.871)、3.809(1.471 ～7.799)、3.853(1.473～6.732)mg/g]、高氟组[高氟组、高氟低砷组、高氟高砷组分别为70.086(46.183～ 131.927)、69.925 (40.503 ～ 96.183)、67.950(52.622 ～ 89.487) mg/g]组间比较差异有统计学意义(P＜0.05).骨砷含量随着砷染毒剂量的增加而升高,其中低砷组[低砷组、低氟低砷组、高氟低砷组分别为7.195(5.060 ～9.860)、6.518(2.960 ～ 12.130)、6.970(3.400 ～9.730)μg/g]、高砷组[高砷组、低氟高砷组、高氟高砷组分别为8.823 (5.760 ～ 10.840)、9.470(7.230～12.860)、8.321(2.420 ～17.540)μg/g]浓度均高于无砷染毒组[对照组、低氟组、高氟组分别为1.785(0.300～3.750)、2.226(1.410～3.980)、2.030(1.040 ～3.850) μg/g],差异有统计学意义(P＜0.05),而低砷组与高砷组骨砷含量差异无统计学意义(P＞0.05).氟与Runx2、MMP-9、Osterix、RANKL蛋白含量间呈正相关(氟染毒量与蛋白含量间相关系数分别为0.647、0.354、0.582和0.613),骨氟含量与蛋白含量间相关系数分别为0.559、0.387、0.487、0.525,P值均＜0.01,砷染毒剂量与Runx2呈负相关(相关系数为-0.527,P＜0.05),与MMP-9、RANKL、Osterix无相关关系(P＞0.05).氟砷联合染毒与Runx2、MMP-9、RANKL、Osterix蛋白含量具有交互效应(F值分别为3.88、15.66、2.92、6.42,P值均＜0.05).结论 氟砷联合暴露对大鼠骨骼代谢Runx2及其下游相关因子的交互作用表现为拮抗作用.
    목적 연구만성불신연합폭로대대서골격대사Runx2급기하유상관인자적영향.방법 장54지8주령청길급SD대서안석인설계방법수궤분성9조,매조6지,자웅각반,분위대조조、저불조、고불조、저신조、고신조、저불저신조、저불고신조、고불저신조급고불고신조.사용불화납(NaF,저불조5mg/kg、고불조20 mg/kg)화아신산납(NaAsO2,저신조2.5 mg/kg、고신조10 mg/kg)관위염독6개월；측정대서골격중Runx2、기질금속단백매9(MMP-9)、성골상관전록인자(Osterix)핵인자-κB수체활화인자배기(RANKL)단백농도.결과 대조조、저신조、고신조무불반아출현,저불조、고불조불반아비례(분별위5/6、6/6)여대조조(O)상비,차이균유통계학의의(x2=8.57、12.00,p＜0.05).골불함량수착불염독제량적증가이승고,무불염독조[대조조、저신조、고신조적궤하균수(최소치～최대치)분별위0.005(0.003 ～0.009)、0.006(0.003～0.021)、0.007(0.002～0.100)mg/g]、저불조[저불조、저불저신조、저불고신조분별위3.395(2.416 ～5.871)、3.809(1.471 ～7.799)、3.853(1.473～6.732)mg/g]、고불조[고불조、고불저신조、고불고신조분별위70.086(46.183～ 131.927)、69.925 (40.503 ～ 96.183)、67.950(52.622 ～ 89.487) mg/g]조간비교차이유통계학의의(P＜0.05).골신함량수착신염독제량적증가이승고,기중저신조[저신조、저불저신조、고불저신조분별위7.195(5.060 ～9.860)、6.518(2.960 ～ 12.130)、6.970(3.400 ～9.730)μg/g]、고신조[고신조、저불고신조、고불고신조분별위8.823 (5.760 ～ 10.840)、9.470(7.230～12.860)、8.321(2.420 ～17.540)μg/g]농도균고우무신염독조[대조조、저불조、고불조분별위1.785(0.300～3.750)、2.226(1.410～3.980)、2.030(1.040 ～3.850) μg/g],차이유통계학의의(P＜0.05),이저신조여고신조골신함량차이무통계학의의(P＞0.05).불여Runx2、MMP-9、Osterix、RANKL단백함량간정정상관(불염독량여단백함량간상관계수분별위0.647、0.354、0.582화0.613),골불함량여단백함량간상관계수분별위0.559、0.387、0.487、0.525,P치균＜0.01,신염독제량여Runx2정부상관(상관계수위-0.527,P＜0.05),여MMP-9、RANKL、Osterix무상관관계(P＞0.05).불신연합염독여Runx2、MMP-9、RANKL、Osterix단백함량구유교호효응(F치분별위3.88、15.66、2.92、6.42,P치균＜0.05).결론 불신연합폭로대대서골격대사Runx2급기하유상관인자적교호작용표현위길항작용.
    Objective To observe the chronic combined effects of sodium fluoride and sodium arsenite on the Runx2 and downstream related factors of bone metabolism in SD rats.Methods SD rats were divided randomly into nine groups of 6 each by factorial experimental design (half female and half male),and supplied with the different doses of fluoride,arsenite and fluoride plus arsenite containing in deionized water(untreated control containing 0 mg/kg fluoride and 0 mg/kg arsenite,and low-fluoride and high supplemented with 5 and 20 mg/kg fluoride,and low-arsenite and high supplemented with 2.5 and 10 mg/kg arsenite,and low-fluoride plus low-arsenite,and low-fluoride plus high-arsenite,and high-fluoride plus low-arsenite,and high-fluoride plus high-arsenite,respectively).After 6 months exposure,the concentration of Runx2,matrix metallopeptidase 9(MMP-9),Osterix,Receptor activator for nuclear factor-κβ ligand (RANKL) were detected by enzyme-linked immunosorbent assay method,respectively.Results There were no dental fluorosis found in the control group,low-arsenic group and high-arsenic group.There were significant differences in the constituent ratio of dental fluorosis among the rats from low-fluoride and high-fluoride (that is 5 rats out of 6 and 6 rats out of 6) compared with the control group (0 rat out of 6) (x2 =8.57,12.00,P ＜ 0.05).The bone fluorine level increased with the increase of fluoride dose,the groups without fluoride supply (control group,low-arsenite and high-arsenite group's geometricmean (minimum-maximum) were 0.005 (0.003-0.009),0.006 (0.003-0.021),0.003 (0.002-0.100)mg/g,respectively),low-fluorine groups (low-fluoride group,low-fluoride plus low-arsenite,and low-fluoride plus high-arsenite group were 3.395 (2.416-5.871),3.809 (1.471-7.799),1.471 (1.473-6.732) mg/g,respectively),the high-fluorine groups (high-fluoride,high-fluoride plus lowarsenite,and high-fluoride plus high-arsenite group were 70.086 (46.183-131.927),69.925 (40.503-96.183),40.503 (52.622-89.487)mg/g,respectively) and the differences between groups was significant (P ＜ 0.05).The bone arsenic level increased with the increase of arsenite dose.The low-arsenic groups (low-arsenite group,low-arsenite plus low-fluoride,and low-arsenite plus high-fluoride group were 7.195 (5.060-9.860),6.518(2.960-12.130),6.970(3.400-9.730) μg/g,respectively),the high-arsenic groups (high-arsenite,high-arsenite plus low-fluoride,and high-fluoride plus high-arsenite group's geometricmean(minimum-maximum) were 8.823 (5.760-10.840),9.470 (7.230-12.860),8.321 (2.420-17.540) μg/g,respectively) were significantly higher than that in the groups without arsenic supply(control group,low-fluoride and high-fluoride group were 1.785 (0.300-3.750),2.226 (1.410-3.980),2.030(1.040-3.850) μg/g,respectively) (P ＜0.05).There was no significant difference of the bone arsenic concentration between low-arsenic and high arsenic group.There was significant positive correlation between fluoride concentration and Runx2,MMP-9,Osterix,RANKL level (the correlation coefficient was 0.647,0.354,0.582,0.613 between fluorine gavage concentration and protein level,the correlation coefficient was 0.559,0.387,0.487,0.525 between bone fluorine concentration and protein level,respectively,P ＜ 0.01).There was negative correlation between arsenite gavage concentration with Runx2 level(r =-0.527,P ＜ 0.05) and was no correlation between arsenite gavage concentration with MMP-9,RANKL,Osterix level (P ＞ 0.05).There was interaction between fluoride and arsenite to Runx2,MMP-9,RANKL,Osterix (F =3.88,15.66,2.92,6.42,respectively,P =0.01,＜ 0.01,0.031,＜ 0.01,respectively).Conclusion The combined effects of fluoride and arsenic on the Runx2,MMP-9,RANKL,Osterix of bone metabolism showed antagonistic effects.
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