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

Effects of maltol aluminum exposure on hippocampus neuroligin 1 and long-term potentiation in rats

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 explore the effects of sub-chronic aluminum exposure on the combination of hippocampus neuroligin 1 （NL1） with N-methyl-D-aspartate receptor （NMDAR） and the effects of correlated bonding to long-term potentiation （LTP） in rats.Methods Ninety healthy male specific pathogen free SD rats were selected and 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 blank control group received no treatment.Rats in solvent control group were given 0.9% sodium chloride solution by concentration of 1 mL/kg body weight （bw）.The low-, medium-and high-dose group rats were given the mass concentration of 0.41, 0.81, 1.62 mg/kg bw maltol aluminum solution by intraperitoneal injection every other day for 1, 2, and 3 months, respectively.After maltol aluminum exposure, LTP was detected in the CA1 region of rat hippocampus, aluminum levels were detected by the graphite furnace atomic absorption spectrometry, and the protein relative expression of NL1 combined with NMDAR1 and NMDAR2B were detected by immunoprecipitation and immunoblotting.Results The LTP in the solvent control group and the low-, medium-, high-dose groups were all lower than that in the blank control group （P〈0.01）.The LTP in the high-dose group was lower than those in the solvent control group and the low-and medium-dose groups （P〈0.05）.The aluminum levels in the hippocampus of rats in the low-, medium-and high-dose groups were higher than those of the blank control group and the solvent control group （P〈0.01）.The protein relative expression of NMDAR1 and NMDAR2B combined with NL1 in treatment groups was lower than those in the blank control group and solvent control group at the same exposure time points （P〈0.01）.The protein relative expression of NMDAR1 and NMDAR2B combined with NL1 in treatment groups at time point of 2 months was lower than those at time point of 1 month in the same dose group （P〈0.01）.The protein relative expression of NMDAR1 and NMDAR2B combined with NL1 at time point of 3 months was lower than those at time points of 1 and 2 months in the same dose group （P〈0.01）.Conclusion Maltol aluminum can prevent the normal combination of NL1 with NMDAR1 and NMDAR2B, affecting LTP regulated by NMDAR1 and NMDAR2B, resulting in a LTP decline, as well as learning and memory impairment.