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目的研究多溴联苯醚-153(BDE-153)对大鼠体内、体外神经细胞内钙离子浓度及其相关激酶活力和含量的影响。方法体内实验:将40只4月龄清洁级雄性SD大鼠按窝别和体重随机分为4组,分别为溶剂对照(橄榄油)组和低(1 mg/kg)、中(5 mg/kg)、高剂量(10 mg/kg)BDE-153染毒组,每组10只。在仔鼠出生第10天,采用一次性腹腔注射方式进行染毒,染毒容量为0.01 ml/g;断乳后(出生第21天)继续饲养2个月。体外实验:将神经细胞分别暴露于含终浓度0(对照)、10、20、40μmol/L BDE-153的培养基染毒48 h。测定仔鼠大脑皮质细胞和神经细胞内钙离子、钙激活中性蛋白酶(calpain)浓度和钙调神经磷酸酶(CaN)、Ca~(2+)-Mg~(2+)-ATP酶的活力。结果体内实验结果显示,与溶剂对照组比较,各剂量BDE-153染毒组仔鼠大脑皮质细胞内钙离子的浓度较低,而calpain的浓度较高,差异均有统计学意义(P<0.05);Ca N和Ca~(2+)-Mg~(2+)-ATP酶的活力均无明显变化。且随着BDE-153染毒剂量的升高,仔鼠大脑皮质细胞内钙离子的浓度呈下降趋势,而calpain的浓度呈上升趋势。体外实验结果显示,与溶剂对照组比较,各浓度BDE-153染毒组神经细胞内钙离子和calpain的浓度均较高,除10μmol/L BDE-153染毒组钙离子浓度外,差异有统计学意义(P<0.05);且随着BDE-153染毒浓度的升高,神经细胞内钙离子和calpain的浓度均呈上升趋势。结论 BDE-153染毒可导致细胞内钙离子和calpain的浓度升高,这可能是BDE-153的神经毒性作用机制之一。
Objective To investigate the effect of polybrominated diphenyl ether-153 (BDE-153) on the concentration of calcium ion and the activity of related kinases in neurons in vivo and in vitro. Methods In vivo experiments: Forty clean male Sprague-Dawley rats of 4 months old were randomly divided into 4 groups according to the litter size and body weight: solvent control (olive oil) group and low (1 mg / kg) kg) and high dose (10 mg / kg) BDE-153. The pups were born on the 10th day, using a one-time intraperitoneal injection of exposure, exposure capacity of 0.01 ml / g; weaning (birth 21 days) to keep feeding 2 months. In vitro experiments: Nerve cells were exposed to medium containing final concentrations of 0 (control), 10, 20, 40 μmol / L BDE-153 for 48 h. The activity of Ca2 +, calpain and Ca2 +, Ca2 + - Mg2 + -ATPase in the cortex and neural cells of the pups were determined . Results The results of in vivo experiments showed that compared with the solvent control group, the intracellular calcium concentration was lower in the cortical pups of BDE-153 group at various doses, while the concentration of calpain was higher, with statistical significance (P <0.05 ); CaN and Ca ~ (2 +) - Mg ~ (2 +) - ATPase activity had no significant change. And with the increase of BDE-153 dose, the intracellular calcium concentration of the offspring rats decreased, while the calpain concentration increased. The results of in vitro experiments showed that compared with the solvent control group, the concentrations of intracellular calcium and calpain were higher in BDE-153 group than in the solvent control group, except for the concentration of calcium ion in 10μmol / L BDE-153 group (P <0.05). With the increase of BDE-153 concentration, the intracellular Ca2 + and calpain concentrations showed an upward trend. Conclusion Exposure of BDE-153 to intracellular Ca2 + and calpain concentrations may be one of the neurotoxic mechanisms of BDE-153.