摘要
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.
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.
出处
《中华预防医学杂志》
CAS
CSCD
北大核心
2013年第9期794-798,共5页
Chinese Journal of Preventive Medicine
基金
国家自然科学基金（81072248）
关键词
氟
砷
大鼠
联合作用
RUNX2
Fluoride
Arsenite
Rats
Combined effects
Runx2
