Sun Yan, Ke Lulu, Zheng Xiangren, Li Tao, Ouyang Wei, Zhang Zigui
College of Chemistry and Life Science, Zhejiang Normal University, Jinhua, 321004, People's Republic of China.
College of Sports and Health Science, Zhejiang Normal University, Jinhua, 321004, People's Republic of China.
Biol Trace Elem Res. 2017 Apr;176(2):355-366. doi: 10.1007/s12011-016-0850-9. Epub 2016 Sep 21.
The purpose of the investigation is to reveal the influence of dietary calcium on fluorosis-induced brain cell apoptosis in rat offspring, as well as the underlying molecular mechanism. Sprague-Dawley (SD) female rats were randomly divided into five groups: control group, fluoride group, low calcium, low calcium fluoride group, and high calcium fluoride group. SD male rats were used for breeding only. After 3 months, male and female rats were mated in a 1:1 ratio. Subsequently, 18-day-old gestation rats and 14- and 28-day-old rats were used as experimental subjects. We determined the blood/urine fluoride, the blood/urine calcium, the apoptosis in the hippocampus, and the expression levels of apoptosis-related genes, namely Bcl-2, caspase 12, and JNK. Blood or blood/urine fluoride levels and apoptotic cells were found significantly increased in fluorosis rat offspring as compared to controls. Furthermore, the Bcl-2 messenger RNA (mRNA) expression levels significantly decreased, and caspase 12 mRNA levels significantly increased in each age group as compared to controls. Compared with the fluoride group, the blood/urine fluoride content and apoptotic cells evidently decreased in the high calcium fluoride group, Bcl-2 mRNA expression significantly increased and caspase 12 mRNA expression significantly decreased in each age group. All results showed no gender difference. Based on these results, the molecular mechanisms of fluorosis-induced brain cell apoptosis in rat offspring may include the decrease in Bcl-2 mRNA expression level and increase in caspase 12 mRNA expression signaling pathways. High calcium intake could reverse these gene expression trends. By contrast, low calcium intake intensified the toxic effects of fluoride on brain cells.
本研究旨在揭示膳食钙对氟中毒诱导的大鼠子代脑细胞凋亡的影响及其潜在分子机制。将Sprague-Dawley（SD）雌性大鼠随机分为五组：对照组、氟组、低钙组、低钙氟组和高钙氟组。仅使用SD雄性大鼠进行繁殖。3个月后，雌雄大鼠按1:1比例交配。随后，将妊娠18天的大鼠以及出生14天和28天的大鼠作为实验对象。我们测定了血/尿氟、血/尿钙、海马体中的细胞凋亡情况以及凋亡相关基因（即Bcl-2、半胱天冬酶12和JNK）的表达水平。与对照组相比，发现氟中毒大鼠子代的血/尿氟水平和凋亡细胞显著增加。此外，与对照组相比，各年龄组中Bcl-2信使核糖核酸（mRNA）表达水平显著降低，而半胱天冬酶12 mRNA水平显著升高。与氟组相比，高钙氟组的血/尿氟含量和凋亡细胞明显减少，各年龄组中Bcl-2 mRNA表达显著增加，半胱天冬酶12 mRNA表达显著降低。所有结果均未显示出性别差异。基于这些结果，氟中毒诱导大鼠子代脑细胞凋亡的分子机制可能包括Bcl-2 mRNA表达水平降低和半胱天冬酶12 mRNA表达信号通路增加。高钙摄入可逆转这些基因表达趋势。相比之下，低钙摄入会加剧氟对脑细胞的毒性作用。
