Effect of Sodium Fluoride on Bone Biomechanical and Histomorphometric Parameters and on Insulin Signaling and Insulin Sensitivity in Ovariectomized Rats
Effect of Sodium Fluoride on Bone Biomechanical and Histomorphometric Parameters and on Insulin Signaling and Insulin Sensitivity in Ovariectomized Rats
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DOI：
10.1007/s12011-016-0642-2
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发表时间：
2016-09-01
影响因子：
3.9
通讯作者：
Sumida, Doris Hissako
中科院分区：
文献类型：
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作者：
Alves Nunes, Rita de Cassia;Chiba, Fernando Yamamoto;Sumida, Doris Hissako
骨质疏松症是一种全身性疾病，其特征是骨降解和骨量减少，促进骨脆性增加和最终骨折风险。研究已经调查了氟化钠（NaF）用于治疗骨质疏松症的用途。然而，氟化物可以改变葡萄糖稳态。本研究的目的是评价从水中摄入NaF（50 mg/L）对去卵巢（OVX）大鼠以下参数的影响：（1）胰岛素受体底物酪氨酸磷酸化状态（2）胰岛素敏感性;（3）葡萄糖、胰岛素、总胆固醇、甘油三酯、TNF-α、IL-6、骨钙素、钙和氟化物的血浆浓度;（4）胫骨中的骨密度和生物力学性质;和（5）胫骨组织形态计量分析。将52只2月龄Wistar大鼠切除卵巢，随机分为对照组（OVX-C）和NaF组（OVX-F）。NaF慢性处理促进（1）pp 185降低（2）胰岛素、氟化物、骨钙素、钙、甘油三酯、VLDL-胆固醇、TNF-α和IL-6的血浆浓度增加;（3）骨小梁宽度、骨面积、刚度、最大强度和韧性降低;（4）体重、食物和水摄入量、血浆葡萄糖、总胆固醇、HDL-胆固醇、LDL-胆固醇、骨矿物质含量和骨矿物质密度无变化。得出的结论是，慢性治疗与氟化钠（50毫克/升）在OVX大鼠的胰岛素敏感性，胰岛素信号转导，生化，生物力学和组织形态计量骨参数的下降。
Osteoporosis is a systemic disease characterized by bone degradation and decreased bone mass that promotes increased bone fragility and eventual fracture risk. Studies have investigated the use of sodium fluoride (NaF) for the treatment of osteoporosis. However, fluoride can alter glucose homeostasis. The aim of this study was to evaluate the effects of NaF intake (50 mg/L) from water on the following parameters of ovariectomized (OVX) rats: (1) tyrosine phosphorylation status of insulin receptor substrate (pp185 (IRS-1/IRS-2)) in white adipose tissue; (2) insulin sensitivity; (3) plasma concentrations of glucose, insulin, total cholesterol, triglyceride, TNF-alpha, IL-6, osteocalcin, calcium, and fluoride; (4) bone density and biomechanical properties in the tibia; and (5) tibia histomorphometric analysis. Fifty-two Wistar rats (2 months old) were ovariectomized and distributed into two groups: control group (OVX-C) and NaF group (OVX-F), which was subjected to treatment with NaF (50 mg/L) administered in drinking water for 42 days. The chronic treatment with NaF promoted (1) a decrease in pp185 (IRS-1/IRS-2) tyrosine phosphorylation status after insulin infusion in white adipose tissue and in insulin sensitivity; (2) an increase in the plasma concentration of insulin, fluoride, osteocalcin, calcium, triglyceride, VLDL-cholesterol, TNF-alpha, and IL-6; (3) a reduction in the trabecular width, bone area, stiffness, maximum strength, and tenacity; (4) no changes in body weight, food and water intake, plasma glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol, bone mineral content, and bone mineral density. It was concluded that chronic treatment with NaF (50 mg/L) in OVX rats causes a decrease in insulin sensitivity, insulin signaling transduction, and biochemical, biomechanical, and histomorphometric bone parameters.