麦芽酚铝暴露对大鼠海马神经连接蛋白1与长时程增强的影响

发布时间：2019-03-27 19:09

【摘要】：目的探讨亚慢性染铝对大鼠海马中神经连接蛋白1(NL1)与N-甲基-D-天冬氨酸受体(NMDAR)结合的影响,以及相关结合对大鼠长时程增强(LTP)的影响。方法取无特定病原体级健康雄性SD大鼠随机分为空白对照组、溶剂对照组和低、中、高剂量组,每组18只。空白对照组大鼠不予任何处理,溶剂对照组大鼠予剂量为1 m L/kg体质量的0.9%氯化钠溶液,低、中、高剂量组大鼠分别予质量浓度为0.41、0.81和1.62 mg/kg体质量的麦芽酚铝溶液,隔日腹腔注射,分别染毒1、2和3个月。染毒结束后,进行大鼠海马CA1区在体LTP测定;取大鼠海马,采用石墨炉原子吸收光谱法测定铝水平,采用免疫共沉淀和免疫印迹法测定与NL1结合的NMDAR1、NMDAR2B蛋白相对表达水平。结果溶剂对照组和低、中、高剂量组大鼠LTP均低于空白对照组(P0.01);高剂量组大鼠LTP分别低于溶剂对照组和低、中剂量组(P0.05)。低、中、高剂量组大鼠海马中铝水平均高于空白对照组和溶剂对照组(P0.01)。各剂量组各时间点大鼠海马中与NL1结合的NMDAR1、NMDAR2B蛋白相对表达水平均低于同时间点空白对照组和溶剂对照组(P0.01)。各剂量组2个月时间点的大鼠海马中与NL1结合的NMDAR1、NMDAR2B蛋白相对表达水平均低于同剂量组1个月时间点(P0.01)。各剂量组3个月时间点大鼠海马中与NL1结合的NMDAR1和NMDAR2B蛋白相对表达水平均低于同剂量组1、2个月时间点(P0.01)。结论麦芽酚铝可阻碍大鼠海马中NL1与NMDAR1和NMDAR2B的正常结合,进而影响NMDAR1和NMDAR2B对LTP的调节使其幅值下降,导致学习记忆损伤。
[Abstract]:Aim to investigate the effects of subchronic aluminum exposure on the binding of nerve junction protein-1 (NL1) to N-methyl-D-aspartic acid receptor (NMDAR) in hippocampus of rats and the effect of related binding on long-term potentiation of (LTP) in rats. Methods healthy male SD rats without specific pathogen grade were randomly divided into blank control group, solvent control group and low, middle and high dose groups with 18 rats in each group. The rats in the control group were given 0.9% sodium chloride solution of 1 m L/kg body mass, low and medium, while the rats in the solvent control group were given 0.9% sodium chloride solution of 1 m body mass without any treatment. The rats in the high dose group were given maltol aluminum solution with body mass of 0.41, 0.81 and 1.62 mg/kg respectively. The rats in the high dose group were injected intraperitoneally every other day for 1, 2 and 3 months, respectively. After exposure, in vivo LTP was measured in CA1 region of rat hippocampus, aluminum level was measured by graphite furnace atomic absorption spectrometry (GFAAS), and relative expression level of NMDAR1,NMDAR2B protein binding to NL1 was determined by immunoprecipitation and immunoblotting. Results the LTP of rats in solvent control group and low, middle and high dose groups were lower than those in blank control group (P0.01), and the LTP in high dose group were lower than those in solvent control group and low and middle dose groups respectively (P0.05). The levels of aluminum in hippocampus of rats in low, middle and high dose groups were higher than those in blank control group and solvent control group (P0.01). The relative expression level of NL1-binding NMDAR1,NMDAR2B protein in hippocampus of rats in each dose group was lower than that in blank control group and solvent control group at the same time (P0.01). The relative expression level of NL1-binding NMDAR1,NMDAR2B protein in hippocampus of rats at 2 months in each dose group was lower than that in the same dose group at 1 month time point (P0.01). The relative expression levels of NL1-binding NMDAR1 and NMDAR2B protein in hippocampus of rats in each dose group were lower than those in the same dose group at 3 months and 2 months (P0.01). Conclusion maltol aluminum can inhibit the normal binding of NL1 to NMDAR1 and NMDAR2B in hippocampus of rats, and then affect the regulation of LTP by NMDAR1 and NMDAR2B, which results in the decrease of LTP amplitude and lead to learning and memory impairment. [WT5 "HZ] conclusion [WT5" BZ]
【作者单位】：山西医科大学公共卫生学院劳动卫生教研室;
【基金】：国家自然科学基金(81430078)
【分类号】：R114

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