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慢性氟中毒对大鼠海马钙离子和 CaMKIIα、c-fos 表达的影响。

The Effect of Chronic Fluorosis on Calcium Ions and CaMKIIα, and c-fos Expression in the Rat Hippocampus.

机构信息

College of Environmental Science and Engineering, Qingdao University, Qingdao, Shandong, China.

College of Chemistry and Life Science, Qingdao Technical College, Qiantangjiang Road, Qingdao, Shandong, 266555, China.

出版信息

Biol Trace Elem Res. 2018 Apr;182(2):295-302. doi: 10.1007/s12011-017-1098-8. Epub 2017 Jul 20.

Abstract

This study investigated neurotoxicity of chronic fluorosis in the rat hippocampus. Newly weaning, male, Sprague-Dawley (SD) rats were administered 15, 30, and 60 mg/L sodium fluoride (NaF) solution (fluorine ion concentration 8.25, 16.50, and 33.00 mg/L, respectively), and tap water, for 18 months. The neurotoxicological mechanism was examined with a focus on intracellular calcium overload. Results showed that as the fluoride concentration increased, calcium ion concentration [Ca], the expression of calcium/calmodulin-dependent protein kinase II α (CaMKIIα), and the expression of catus proto-oncogene protein c-fos (c-fos) all tend to increase. Compared to the control group, Ca, CaMKIIα, and c-fos significantly increased (P < 0.05) in the moderate-fluoride and the high-fluoride groups. These results indicate that Ca/CaMKIIα/c-fos channel signal may be the molecular mechanism of central nervous system damage caused by chronic fluoride intoxication. Moreover, elevated Ca concentration in the hippocampus may be the initiating factor of neuronal apoptosis induced by fluoride.

摘要

本研究探讨了慢性氟中毒对大鼠海马的神经毒性。新生雄性 Sprague-Dawley (SD) 大鼠给予 15、30 和 60 mg/L 氟化钠 (NaF) 溶液(氟离子浓度分别为 8.25、16.50 和 33.00 mg/L)和自来水,持续 18 个月。神经毒理学机制的研究重点是细胞内钙超载。结果表明,随着氟浓度的增加,钙离子浓度 ([Ca])、钙/钙调蛋白依赖性蛋白激酶 IIα (CaMKIIα) 的表达和 c-fos 原癌基因蛋白 (c-fos) 的表达均趋于增加。与对照组相比,中氟组和高氟组 Ca、CaMKIIα 和 c-fos 显著增加 (P<0.05)。这些结果表明 Ca/CaMKIIα/c-fos 通道信号可能是慢性氟中毒引起中枢神经系统损伤的分子机制。此外,海马中 Ca 浓度的升高可能是氟诱导神经元凋亡的起始因素。

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