摘要
目的探讨不同饲料钙水平对母鼠氟暴露致仔鼠海马神经细胞凋亡的影响及分子机制。方法选用SD大鼠100只,75只雌鼠随机分为对照组(Con)、高氟组(F)、低钙组(LCa)、高氟低钙组(F+LCa)和高氟高钙组(F+HCa),饲养3月后,雌雄鼠合笼交配产仔鼠,取14、28日龄仔鼠2批,以海马CA3区神经细胞凋亡及凋亡信号通路相关蛋白Bcl-2、Caspase12和JNK表达水平为观测指标。结果母鼠氟暴露后,28日龄雌雄海马细胞凋亡指数显著(P<0.05)升高;14、28日龄雌雄仔鼠海马凋亡信号通路中Bcl-2蛋白表达均呈现极显著(P<0.01)下调,而14日龄雄仔鼠和28日龄雌仔鼠的Caspase12、14和28日龄雌雄仔鼠JNK蛋白表达水平均呈极显著(P<0.01)上调,14日龄雌仔鼠和28日龄雄仔鼠的Caspase12仅呈显著(P<0.05)上调;饲料低钙加剧母鼠氟暴露后仔鼠海马神经细胞凋亡,Bcl-2蛋白表达水平进一步下降,Caspase12和JNK蛋白表达水平进一步上升;而饲料高钙能够缓解母鼠氟暴露致仔鼠海马神经细胞的凋亡,逆转上述3者的蛋白表达水平;所检测的上述3个凋亡相关蛋白中,只有Caspase12表达水平呈性别和日龄差异,饲料钙对母鼠氟暴露致14日龄雄仔鼠和28日龄雌仔鼠Caspase12表达水平变化分别较同一日龄另一性别仔鼠的影响更大。结论海马凋亡信号通路中Bcl-2、Caspase12和JNK蛋白表达水平的变化可能是钙对母鼠氟暴露致子代大鼠大脑神经细胞凋亡影响的分子机制之一。饲料钙对母鼠氟暴露致14、28日龄仔鼠海马凋亡信号通路Caspase12表达水平变化的影响呈一定的性别差异,其机制有待于进一步阐明。
Objective To investigate the effects of calcium on fluorosis-induced neuronal apoptosis in hippocampus and its molecular mechanism in offspring rats. Methods A total of 75 female rats were randomly divided into control group （Con）, high fluorine group （F）, low calcium group （LCa）, low calcium and high fluoride group （LCa＋F） and calcium fluoride group （HCa＋F）.After exposing to fluoride for 3 months, male and female rats mated. The offsprings aged 14 and 28 days were taken as experimental subjects. The expression levels of proteins in CA3 of hippocampus, namely, Bcl-2, Caspasel2 and JNK were detected. Results After maternal exposure to fluoride, the apoptosis index of male and female hippocampal cells at 28 days was significantly higher （P〈0.05）.The expression of Bcl-2 protein in the hippoeampus was significantly down-regulated （P〈0.01） in 14-day-old and 28-day-old mice. The expression of Caspasel2 protein in 14-day-old male mice and 2g-day-old femal mice, and the expression level of JNK protein in 14-day-old and 28-day-old pups were significantly （P〈0.01） up-regulated. The expression of Caspasel2 protein was significantly up-regulated （P〈0.05） in 14-day-old female mice and 28-day male pups.Low dietary calcium exacerbated neuronal apoptosis in the hippocampus of the pups after exposed to fluoride exposure, and the Bcl-2 protein expression level was decreased further. The expression levels of Caspasel2 andJNK proteins were further increased. The feed high in calcium alleviated the apoptosis of hippocampal neurons induced by fluoride exposure in the mother rats and reversed the protein expression levels of the above three genes. Among the three apoptosis-related proteins, only the expression level of Caspase12 was related to gender and age. The change of Caspase 12 expression in the 14-day male and 28-day female mice exposed to calcium diets was greater than that in the same day-old infants. Conclusion The changes of protein Bcl-2, Caspase12 and JNK expression levels of apoptosis pathway in hippocampus, may be one of the molecular mechanisms for the action of dietary calcium on fluorosis-induced neuronal apoptosis in the hippocampus of offspring rats. The effect of dietary calcium on Caspase12 expression level in the hippocampus of 14-day-old and 28-day-old mice after maternal exposure to fluoride is gender dependent. The mechanism needs further investigation.
作者
年未未
汪晓宇
邵丹丹
于秋丽
欧阳玮
章子贵
NIAN Wei-wei;WANG Xiao-yu;SHAO Dan-dan;YU Qiu-li;OUYANG Wei;ZHANG Zi-gui(College of Chemistry and Life Science at Zhejiang Normal Universitye,Jinhua 321004;Physical Education College and Health Science of 3 Zhejiang Normal University,Jinhua 321004;Zhejtang Normal University Xingzhi College,Jinhua 321004,China)
出处
《营养学报》
CAS
CSCD
北大核心
2018年第5期470-476,482,共8页
Acta Nutrimenta Sinica
基金
国家自然科学基金(No.81573101)
