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氟对去卵巢大鼠胰岛素信号传导和骨代谢的影响。

Effects of fluoride on insulin signaling and bone metabolism in ovariectomized rats.

作者信息

Pereira Amanda Gomes, Chiba Fernando Yamamoto, de Lima Coutinho Mattera Maria Sara, Pereira Renato Felipe, de Cássia Alves Nunes Rita, Tsosura Thaís Verônica Saori, Okamoto Roberta, Sumida Doris Hissako

机构信息

Programa de Pós-Graduação Multicêntrico em Ciências Fisiológicas-SBFis - Department of Basic Sciences - Araçatuba Dental School, UNESP - Univ Estadual Paulista, Rua José Bonifácio 1193. CEP 16015-050, Brazil.

Department of Child and Social Dentistry - Araçatuba Dental School, UNESP - Univ Estadual Paulista, Rua José Bonifácio 1193. CEP 16015-050, Brazil.

出版信息

J Trace Elem Med Biol. 2017 Jan;39:140-146. doi: 10.1016/j.jtemb.2016.09.007. Epub 2016 Sep 23.

DOI:10.1016/j.jtemb.2016.09.007
PMID:27908407
Abstract

Fluoride is an essential trace element for the maintenance of bone health owing to its capacity to stimulate proliferation and osteoblastic activity that can lead to increased bone formation. However, excessive sodium fluoride (NaF) intake can impair carbohydrate metabolism thereby promoting hyperglycemia, insulin resistance, and changes in insulin signaling. Thus, this study aimed to evaluate the effect of chronic treatment with NaF in bone metabolism, insulin signaling, and plasma concentrations of glucose, insulin, tumor necrosis factor-α (TNF-α), osteocalcin (OCN), and fluoride in ovariectomized rats. Thirty-two ovariectomized Wistar rats were randomly distributed into two groups: Control (OVX-C) and those undergoing treatment with NaF (50mg F/L) in drinking water for 42days (OVX-F). Glucose and insulin levels were assessed, followed by homeostasis model assessment of insulin resistance (HOMA-IR). Akt serine phosphorylation was evaluated by western blotting. Plasma concentrations of TNF-α and OCN were evaluated by ELISA. The left and right tibia was collected for immunohistochemical and histomorphometric analysis, respectively. Chronic treatment with NaF promoted insulin resistance, decreased insulin signal, increased plasma concentration of insulin, fluoride, OCN and TNF-α, decreased trabecular bone area of the tibia, and caused changes in bone metabolism markers in ovariectomized rats. These results suggest the need for caution in the use of NaF for the treatment of osteoporosis, especially in postmenopausal woman.

摘要

氟化物是维持骨骼健康所必需的微量元素,因为它能够刺激增殖和成骨细胞活性,从而增加骨形成。然而,过量摄入氟化钠(NaF)会损害碳水化合物代谢,进而导致血糖升高、胰岛素抵抗以及胰岛素信号传导的改变。因此,本研究旨在评估在去卵巢大鼠中,长期使用NaF治疗对骨代谢、胰岛素信号传导以及血浆中葡萄糖、胰岛素、肿瘤坏死因子-α(TNF-α)、骨钙素(OCN)和氟化物浓度的影响。将32只去卵巢的Wistar大鼠随机分为两组:对照组(OVX-C)和饮用含NaF(50mg F/L)水42天的治疗组(OVX-F)。评估葡萄糖和胰岛素水平,随后进行胰岛素抵抗的稳态模型评估(HOMA-IR)。通过蛋白质印迹法评估Akt丝氨酸磷酸化。通过酶联免疫吸附测定法评估血浆中TNF-α和OCN的浓度。分别收集左、右胫骨用于免疫组织化学和组织形态计量学分析。长期使用NaF治疗可导致去卵巢大鼠出现胰岛素抵抗、胰岛素信号降低、血浆胰岛素、氟化物、OCN和TNF-α浓度升高、胫骨小梁骨面积减少以及骨代谢标志物改变。这些结果表明,在使用NaF治疗骨质疏松症时需要谨慎,尤其是在绝经后女性中。

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