大鼠孕期高糖饮食对子代成年骨密度及血清骨代谢指标的影响

The effect of maternal high sucrose exposure on bone mineral density and serum bone metabolism markers in adult offspring

目的研究孕期母体高糖饮食对成年子代大鼠骨密度、骨代谢生化指标及骨保护素(osteoprotegerin, OPG)、核因子-κB受体活化因子配体(receptor activator of NF-κB ligand, RANKL)表达的影响。方法以孕期母鼠给予20%蔗糖水的成年子代雄性大鼠为高糖组,孕期母鼠正常饮水的成年子代雄性大鼠为对照组,用酶联免疫吸附法(ELISA)检测血清胰岛素、碱性磷酸酶(alkaline phosphatase, ALP)、骨钙素、抗酒石酸酸性磷酸酶5b(tartrate resistant acid phosphatase-5b, TRACP-5b)、OPG和RANKL浓度,采用微焦点断层计算机扫描术(Micro-CT)检测2组骨密度,运用实时定量PCR方法检测2组大鼠腰椎组织中OPG和RANKL mRNA表达。结果高糖组大鼠的孕鼠血糖和血胰岛素水平均高于对照组(P<0.05),高糖组孕鼠增重和胎鼠体重均高于对照组(P<0.05)。与对照组相比,高糖组子代大鼠血清ALP、OPG下降,TRACP-5b、RANKL升高,血清OPG/RANKL比值下降(P<0.05)。高糖组子代大鼠腰椎骨密度、骨体积分数、平均骨小梁厚度和平均骨小梁数量也显著低于对照组(P<0.05)。而高糖组子代骨小梁分离度显著高于对照组(P<0.05)。高糖组大鼠腰椎组织OPG mRNA表达显著下调,RANKL mRNA表达较对照组显著上调。结论孕期高糖饮食刺激可能影响OPG系统而改变骨质代谢,导致骨量丢失。

Objective To study the impact on bone mineral density, serum bone metabolism markers, and the expression of osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) in the adult offspring exposed to maternal high sucrose diet during gestation.Methods The pregnant Sprague-Dawley (SD) rats were randomly divided into two groups: high sucrose diet group (HS group) rats were given 20% sucrose solution and standard rat food, normal diet group (ND group) rats were provided with fresh tap water and standard rat food. The serum concentrations of alkaline phosphatase (ALP), osteocalcin, tartrate resistant acid phosphatase-5b (TRACP-5b), OPG, and RANKL were measured by the enzyme linked immunosorbent assay (ELISA). The lumbar vertebrae were attained and prepared for micro-computed tomography (Micro-CT) scanning. Compared the expression of OPG and RANKL mRNA in the adult lumbar vertebrae were determined by realtime quantitative PCR.Results The maternal blood glucose levels and insulin levels were higher in the HS group(P<0.05). The body weight gain during pregnancy and fetal body weight were heavier in the HS group(P<0.05). In HS group that compared to ND group, the serum concentrations of ALP and OPG were decreased, while TRACP-5b and RANKL were increased, and the ratio of OPG/RANKL were significantly increased(P<0.05). Compared to ND group, the bone mineral density, the bone volume per tissue volume, trabecular thickness, the trabecular number were decreased in HS group(P<0.05). The trabecular separation was increased in HS group compared to ND group(P<0.05). The expression of OPG mRNA in the offspring lumbar vertebrae was significantly down-regulated. Conversely, the expression of RANKL mRNA was significantly up-regulated.Conclusion Maternal high sucrose diet during gestational periods may affect the bone mineral density, serum bone metabolism markers, and the expression of OPG and RANKL in adult offspring.