内质网应激在不同钙水平下对母鼠氟暴露后仔鼠脑海马细胞的作用

Effects of Endoplasmic Reticulum Stress on Hippocampus of Offspring Rats with Maternal Fluoride Exposure at Different Calcium Levels

为探讨内质网应激在不同饲料钙水平下对母鼠氟暴露后仔鼠脑海马细胞的作用,选用SD雌性大鼠75只,雄性大鼠25只,雌鼠随机分为对照组(DZ)、染氟组(RF)、低钙组(LG)、染氟低钙组(LF)和染氟高钙组(HF)。雌鼠染毒3个月,交配产仔,检测胎鼠与14日龄、28日龄仔鼠脑海马内质网应激伴侣分子BIP、CHOP和CRT蛋白表达水平。结果显示,与DZ组比,胎鼠、14日龄仔鼠RF组、LF组BIP、CHOP和CRT蛋白表达均显著升高,差异具有统计学意义(P <0.01),HF组BIP、CHOP和CRT蛋白表达均升高,差异具有统计学意义(P <0.05),28日龄仔鼠RF组BIP、CHOP蛋白表达显著升高,差异具有统计学意义(P <0.01),CRT蛋白表达升高,差异具有统计学意义(P <0.05),LF组BIP、CHOP和CRT蛋白表达均显著升高,差异具有统计学意义(P <0.01),HF组BIP、CHOP和CRT蛋白表达均显著升高,差异具有统计学意义(P <0.05)。与RF组比,胎鼠与14日龄、28日龄仔鼠LF组BIP、CHOP和CRT蛋白表达水平升高,差异具有统计学意义(P <0.01),胎鼠、14日龄仔鼠HF组BIP、CHOP和CRT蛋白表达水平下降,差异具有统计学意义(P <0.05),28日龄仔鼠BIP、CHOP蛋白表达水平下降,差异具有统计学意义(P <0.05)。研究表明,内质网应激可能参与了母鼠氟暴露致仔鼠脑损伤,高钙饲料可缓解母鼠氟暴露致仔鼠脑海马神经细胞的损伤,低钙饲料则进一步加剧了母鼠氟暴露致仔鼠脑海马神经细胞损伤。

To investigate the effects of calcium on fluorosis-induced neuronal endoplasmic reticulum stress in hippocampus of offspring rats. Seventy-five healthy early-weaned SD female rats and twenty-five male rats were used for mating. Female rats were randomly divided into control group(DZ group), fluoride group(RF group), low calcium group(LG group), fluoride and low calcium group(LF group), and fluoride and high calcium group(HF group). After 3 months of feeding, male and female rats were mated and the expression levels of stress partner molecules BIP, CHOP, and CRT protein of hippocampus in fetus and in their litters at 14 or 28 days of age were tested.Compared with the DZ group, the expression of BIP, CHOP and CRT protein of fetus and 14-day-old pups in the RF group, the HF group and the LF group were significantly increased(P <0.01 or P <0.05), the expression of BIP and CHOP protein in the RF group and the expression of BIP, CHOP and CRT protein in the LF group of 28-dayold rats were significantly increased(P <0.01), the expression of CRT protein in the RF group were increased(P <0.05). Compared with the RF group, the expression of BIP, CHOP and CRT in the LF group of fetus, 14 and 28-day-old rats were significantly increased(P <0.01), the expression of CHOP and CRT protein in the HF group of fetus and 14-day-old pubs and the expression of BIP and CHOP protein in 28-day-old pubs were decreased(P <0.05). It is indicated that endoplasmic reticulum stress is involved in brain damage induced by fluoride exposure in neonates, high calcium diet can relieve damage of neonatal rat hippocampus induced by fluoride exposure, low calcium diet further exacerbated the damage of hippocampus induced by the maternal rats exposure to fluoride.