多溴联苯醚-153染毒对大鼠神经细胞内钙离子浓度及其相关激酶活力和含量影响的体内和体外实验研究  

Effects of BDE-153 on intracellular Ca^(2+) concentration and Ca^(2+)-related kinase activity and content of neural cells of rats: in vivo and in vitro studies

作　　者：郝忠锁 常利军[1] 张华俊[1] 张红梅[1] HAO Zhong-suo CHANG Li-jun ZHANG Hua-jun ZHANG Hong-mei(Department of Environmental Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, China)

机构地区：[1]山西医科大学公共卫生学院环境卫生教研室,山西太原030001

出　　处：《环境与健康杂志》2016年第11期946-949,共4页Journal of Environment and Health

基　　金：国家自然科学基金(81001258);山西省高等学校优秀青年学术带头人支持计划(晋教财[2011]205号);山西省高等学校科技创新项目(2016155);山西省科技研究基金(2013021033-3)

摘　　要：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 understand the effect of polybrominated diphenyl ethers-153（BDE-153） on the intracellular Ca^2＋ concentration and Ca^2＋-related kinase activity and content of rats＇ neural cells in vivo and in vitro. Methods Experiment in vivo： forty SPF male rats aged four months were randomly divided into four groups by litters and weights： solvent control（olive oil） group,BDE-153-treated groups at the dose of 1 mg/kg, 5 mg/kg and 10 mg/kg body weight,10 rat pups per group. At post natal day10, rat pups were administrated with BDE-153 solvent solution at 0.01 ml/g body weight via intraperitoneal injection once, then were raised continuously for two months after weaning（21 days）. Experiment in vitro： primary cultured neurons were exposed to the final concentration 0（control）, 10, 20 and 40 μmol/L BDE-153 medium for 48 h. The concentration of Ca^2＋,calcium-activated neutral protease（calpain） content and the vitality of Ca N, Ca^2＋-Mg^2＋-ATP of puppy rat cerebral cortex and nerve cells were measured. Results In vivo, compared with solvent control group, in each group of BDE-153 treatment, the intracellular Ca^2＋ concentration of cerebral cortex was lower, the content of calpain was higher, the differences were statistically significant（P〈0.05） with dose-dependent manner. The activities of Ca N and Ca^2＋-Mg^2＋-ATPase did not change at any dose（P〈0.05）. In vitro, compared with the solvent control group, in each group of BDE-153 treatment, in the nerve cell, the Ca^2＋ concentration and calpain content was higher, in addition to the 10 μmol/L BDE-153 group, the differences was statistically significant（P〈0.05）, with dose-dependent manner. Conclusion BDE-153 exposure can increase intracellular Ca^2＋ concentration and calpain content, this may be involved in BDE-153 induced neurotoxicity.

关 键 词：多溴联苯醚-153 钙离子浓度 钙相关激酶 神经毒性 

分 类 号：R994.6[医药卫生—毒理学]