AMPA受体棕榈酰化在亚慢性铝染毒大鼠海马长时程增强中的作用  

Effect of AMPA receptor palmitoylation modification on long-term potentiation in rat hippocampus by subchronic exposure to aluminum

作　　者：夏欣宇 王翡 高婷 宋静[1] XIA Xin-yu;WANG Fei;GAO Ting;SONG Jing(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,山西太原030001

出　　处：《环境与职业医学》2018年第12期1083-1088,共6页Journal of Environmental and Occupational Medicine

基　　金：山西医科大学博士启动基金(编号:03201413)

摘　　要：[目的]研究α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体棕榈酰化修饰在亚慢性铝染毒在大鼠海马长时程增强(LTP)中的作用。[方法]健康成年雄性SD大鼠24只,按体重相近者随机分为对照组、低剂量组、中剂量组、高剂量组,每组6只,采用腹腔注射麦芽酚铝的方式对大鼠进行染毒,对照组给予生理盐水,低、中、高剂量组的铝染毒剂量分别为10、20、40μmol/kg,隔天染毒,共染毒12周。染毒结束后采用在体海马CA1区LTP记录技术,记录兴奋性突触后电位,然后断头取海马,采用酰基生物素置换法测定AMPA受体棕榈酰化水平。[结果] LTP检测结果显示,高频刺激后1 min和60 min时,各剂量组的标准化幅值(后简称"幅值")差异有统计学意义(P<0.05);30 min时差异无统计学意义。1 min时,中、高剂量组的幅值低于对照组和低剂量组,差异均有统计学意义(P<0.05)。60 min时,低、中、高剂量组的幅值均低于对照组,且高剂量组的幅值低于低、中剂量组,差异均有统计学意义(P<0.05)。酰基生物素置换法结果显示,中、高剂量组的离子型谷氨酸受体1(GluR1)低于对照组,差异有统计学意义(P<0.05);中剂量组的离子型谷氨酸受体2(GluR2)棕榈酰化水平低于对照组,高剂量组的GluR2棕榈酰化水平低于对照组及低、中剂量组,差异均有统计学意义(P<0.05)。[结论]亚慢性铝染毒后,大鼠海马LTP受到抑制,AMPA受体棕榈酰化水平降低,这提示AMPA受体棕榈酰化降低可能是LTP损害的机制之一。[Objective] To study the effect of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor palmitoylation modification on long-term potentiation in rat hippocampus by subchronic exposure to aluminum.[Methods] Twenty-four healthy adult male SD rats were randomly divided by weight into control group, low-dose group, middledose group, and high-dose group, and administered with saline (control group) or Al(mal)3 (10, 20, and 40μmol/kg) via intraperitoneal injection every two days for 12 weeks. Field excitatory post-synaptic potentials in CA1 region were recorded by field LTP record technique in vivo, and AMPA receptor palmitoylation was examined by acyl-biotin exchange method.[Results] The results of LTP record showed that the standardized amplitude (hereinafter referred to as "amplitude") of each group was significantly different at 1 min and 60 min after high frequency stimulation (P < 0.05), but not at 30 min. The amplitudes of the middle-and high-dose groups were statistically lower than those of the control group and the low dose group at 1min (P < 0.05). The amplitudes of the three dose groups were significantly lower than that of the control group at 60 min, and the amplitude of the high-dose group was significantly lower than those of the low-and middle-dose groups at 60 min (P < 0.05). The results of acyl-biotin exchange showed that the glutamate receptor 1 (GluR1) palmitoylation levels of the middle-and high-dose groups were statistically lower than that of the control group (P < 0.05); the glutamate receptor 2 (GluR2) palmitoylation level in the middle-dose group was statistically lower than that of the control group, and the GluR2 palmitoylation level in the high-dose group was statistically lower than those of the control, low-dose, and middle-dose groups (P < 0.05).[Conclusion] Long-term potentiation in rat hippocampus is inhibited and palmitoylation of AMPA receptor is reduced after subchronic aluminum exposure, suggesting that the reduction of palmitoylation of AMPA receptor may be one

关 键 词：铝 长时程增强 棕榈酰化 AMPA受体 GLUR1 GLUR2 

分 类 号：R114[医药卫生—卫生毒理学]