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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(P<0.01);高剂量组大鼠LTP分别低于溶剂对照组和低、中剂量组(P<0.05)。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(P<0.01)。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(P<0.01)。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(P<0.01)。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(P<0.01)。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。
Objective To investigate the effect of subchronic aluminum exposure on the binding of Nervein 1 (NL1) and N-methyl-D-aspartate receptor (NMDAR) in rat hippocampus, LTP). Methods Healthy male SD rats without specific pathogen were randomly divided into blank control group, solvent control group and low, medium and high dose groups, with 18 rats in each group. The rats in the blank control group were treated with 0.9% sodium chloride solution at the dose of 1 m L / kg body weight and the rats in the low, medium and high dose groups were given 0.41 and 0.81 And 1.62 mg / kg body weight of malt extract aluminum solution, intraperitoneal injection every other day, respectively, exposure to 1,2 and 3 months. Rat LTP was measured in rat hippocampal CA1 region after the end of treatment. The hippocampus of rats were taken out. The levels of aluminum were determined by graphite furnace atomic absorption spectrometry. The co-immunoprecipitation and immunoblotting were used to detect the expression of NMDAR1 and NMDAR2B The expression level. Results The LTP in the solvent control group and the low, medium and high dose groups were lower than those in the blank control group (P <0.01). The LTP in the high dose group was lower than that of the solvent control group and the low and medium dose groups (P <0.05) . The levels of aluminum in hippocampus of rats in low, middle and high dose groups were higher than that of blank control group and solvent control group (P <0.01). The relative expression levels of NMDAR1 and NMDAR2B in the hippocampus of rats at each time point in each dose group were lower than those in the blank control group and the solvent control group at the same time point (P <0.01). The relative expression levels of NMDAR1 and NMDAR2B in the hippocampus of rats in each dose group at 2 months were lower than those in the same dose group for 1 month (P <0.01). The relative expression levels of NMDAR1 and NMDAR2B in the hippocampus of rats in each dose group for 3 months were lower than those in the same dose group for 1 and 2 months (P <0.01). Conclusion Maltool aluminum can block the normal binding of NL1 to NMDAR1 and NMDAR2B in rat hippocampus, and then affect the regulation of LTP by NMDAR1 and NMDAR2B to decrease the amplitude and lead to learning and memory impairment.