氟铝联合中毒对小鼠骨代谢生物标志物的影响

目的 分析氟铝联合染毒小鼠骨代谢标志物的变化,探讨氟铝联合对骨毒性效应的特征和机制.方法 采用2因素3水平析因设计方法将昆明种小鼠分成9组,由氟化钠(NaF,0、50、150mg/L)、氯化铝(AlCl3,0、200、600 mg/L)经饮水染毒,24周后采集血清、尿液,测定血清钙(Ca)、磷(P)、镁(Mg)、碱性磷酸酶(ALP)、骨钙素(BGP)、甲状旁腺激素(PTH)及尿Ca、P.结果 氟铝联合对血清Ca、BGP和尿Ca的影响存在交互作用(F值分别为17.370、4.399、9.448,P<0.01),对血清P、Mg、ALP、PTH和尿P的影响不存在交互作用(F值分别为0.416、0.415、1.921、1.362、1.630,P0.05).高氟组血清Ca[(1.13±0.27)mmoL/L]、BGP[(6.56±5.74)μg/L]比对照组[(1.82±0.37)mmol/L、(23.45±15.40)μg/L]降低(P<0.05),高氟低铝组升高到(1.76±0.36)mmol/L、(10.57±4.28)μg/L,高氟高铝组升高到(2.10±0.51)mmoL/L、(15.73±3.15)μg/L;低氟组尿Ca[(6.24±2.61)mmol/mmol Cr]比对照组[(3.12±2.04)mmol/mmol Cr]升高(P<0.05),与低铝、高铝联合时降低[(0.81±0.44)、(1.23±0.41)mmol/mmol Cr],联合作用与氟单独效应相反.高铝组血清Ca为(1.07±0.68)mmol/L、BGP为(7.21±5.22)μg/L.低氟高铝组升高到(1.47±0.18)mmol/L、(10.98±4.35)μg/L,高氟高铝组升高到(2.10±0.51)mmoL/L、(15.73±3.15)μg/L,联合作用对BGP的影响与铝单独作用随剂量增高的效应趋势相同.结论 本实验条件下,铝拮抗氟对部分骨代谢标志物的作用,氟则促进铝的作用,氟铝联合染毒时骨代谢标志物均降低,联合作用抑制骨形成和骨矿化过程,造成骨代谢紊乱.

Joint effects of fluoride and aluminum on biomarkers of bone metabolism in mice

Objective To explore the interaction characters of fluoride and aluminum by analyzing the changes of bone metabolism in mice. Methods Kunming mice were randomly divided into nine groups according to the factorial experiment, design of two factors and three levels. The animals in different groups were fed with various doses of fluoride(NaF, 0,50,150 mg/L) and/or aluminum(AlCl3, 0,200,600 mg/L) in drinking water for 24 weeks. Serum calcium, phosphor, magnesium, alkaline phosphatase, osteoealine, parathyroid, and urinary calcium and phosphor were tested. Results We found interaetians of fluoride and aluminum with serum calcium, osteoealine and urine calcium(F=17.370,4.399,9.448, P<0.01), but not with serum phosphor, magnesium, alkaline phosphatase, parathyroid or urinary phospbor(F=0.416,0.415,1.921,1.362, 1.630, P 0.05). The serum levels of calcium and osteoealine in high fluoride group were (1.13±0.27)mmol/L and (6.56±5.74)μg/L, respectively, which were lower than in the control group[ (1.82±0.37)mmol/L and (23.45±15.40)laeJL, respectively], but the levels were elevated to (1.76±0.36)mmol/L and (10.57±4.28)μg/L when high fluoride was combined with low aluminum, and further elevated to (2.10±0.51)mmol/L and (15.73±3.15)μg/L when high fluoride was combined with high aluminum. The urinary calcium level in low fluoride group [ (6.24±2.61)retool/retool Cr] was higher than that in the control group[ (3.12±2.04)retool/retool Cr], but it was decreased in low fluoride and aluminum groups[ (0.81±0.44), (1.23± 0.41)mmol/mmoi Cr, respectively]. On the other hand, the levels of serum ealeium and osteocaline in high aluminum group were (1.07±0.68)mmol/L and (7.21±5.22)μg/L, elevated to (1.47±0.18)mmol/L and (10.98±4.35) μg/L when low fluoride was combined wth high aluminum, and further elevated to (2.10±0.51)mmol/L and (15.73± 3.15)μg/L when high fluoride was.combined with high aluminum, respectively, and the combined effects showed the same trend of higher aluminum. Conclusions Aluminum antagonized fluoride-induced effects, whereas fluoride aggravated the effects caused by aluminum in this experimental conditions. The biomarkers of bone formation and mineralization were suppressed in the combined groups, so the combined effects could interfere with the course of bone turnover by inhabiting bone formation and mineralization, leading to the disorder of bone metabolism eventually.