亚慢性染铝对大鼠海马PSD95及长时程增强的影响  

Effects of subchronic aluminum exposure on PSD95 and long-term potentiation in hippocampus of rats

作　　者：高婷 夏欣宇 袁春满 宋静[1] GAO Ting;XIA Xin-yu;YUAN Chun-man;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

出　　处：《环境与职业医学》2019年第11期995-1000,共6页Journal of Environmental and Occupational Medicine

基　　金：山西医科大学博士启动基金（03201413）

摘　　要：[背景]铝广泛存在于环境中,是一种确定的神经毒物。已有大量研究证明铝会损害大鼠海马的长时程增强(LTP),但其机制尚不明了。[目的]研究亚慢性染铝对大鼠海马突触后致密蛋白95(PSD95)以及LTP的影响。[方法]清洁级的健康成年雄性SD大鼠24只,按照体重随机分为4组,分别是对照组、低/中/高剂量麦芽酚铝染毒组,每组6只。对大鼠进行隔天腹腔注射染毒,对照组注射生理盐水,麦芽酚铝染毒组分别注射10、20、40μmoL/kg的麦芽酚铝,持续12周。染毒结束后采用在体电生理法检测海马CA1区LTP,记录场兴奋性突触后电位(fEPSP);然后断头取海马,采用Western blotting检测PSD95蛋白相对表达水平,采用免疫沉淀-酰基生物素置换法检测PSD95蛋白棕榈酰化水平。[结果]大鼠海马CA1区LTP结果显示,各组间大鼠基础波的fEPSP标准化幅值(简称"幅值")差异没有统计学差异(P> 0.05),高频刺激后1、30、60 min,各组大鼠的幅值有差异(P <0.05)。1 min和60 min时,低、中、高剂量组大鼠的幅值均低于对照组(P <0.05),中、高剂量组大鼠的幅值低于低剂量组(P <0.05),高剂量组大鼠的幅值低于中剂量组大鼠(P <0.05)。30 min时,低、中、高剂量组大鼠的幅值均低于对照组(P <0.05),中、高剂量组大鼠的幅值低于低剂量组(P <0.05)。Western blotting结果显示,低、中、高剂量组大鼠的PSD95蛋白相对表达水平分别为0.84±0.08、0.76±0.17、0.68±0.19,均低于对照组(1.00±0.00)(P <0.05)。免疫沉淀-酰基生物素置换法结果显示,对照组、低/中/高剂量组的PSD95蛋白的棕榈酰化水平分别是0.66±0.20、0.55±0.11、0.37±0.11、0.36±0.15,中、高剂量组的PSD95蛋白棕榈酰化水平低于对照组(P <0.05)。[结论]亚慢性铝染毒可导致大鼠海马PSD95蛋白表达水平及棕榈酰化水平降低,可能是铝损害LTP的机制之一。[Background] Aluminum is environmentally abundant in our biosphere and an identified neurotoxicant. A number of studies have shown that aluminum damages long-term potentiation(LTP) in the hippocampus of rats, but the mechanism is not clear.[Objective] This in vivo experiment investigates the effects of subchronic aluminum exposure on postsynaptic density protein 95(PSD95) and LTP in the hippocampus of rats.[Methods] Twenty-four healthy Sprague-Dawley male rats were randomly divided into control group, low-dose aluminum group, medium-dose aluminum group, and high-dose aluminum group according to body weight, with six rats in each group. Via intraperitoneal injection every two days, the control group was administered with saline, and the aluminum groups were injected with 10, 20, or 40 μmoL/kg Al(mal)3 for 12 weeks. The field excitatory post-synaptic potential(fEPSP) in CA1 region was recorded by field potentiation technique in vivo. The hippocampal PSD95 protein relative expression was examined by Western blotting. The level of palmitoylated PSD95 was determined by immunoprecipitation-acyl biotin replacement.[Results] The LTP results in CA1 region in hippocampus of rats showed that the amplitudes of f EPSP in each group were similar at baseline(P > 0.05), but different at 1, 30, and 60 min after high-frequency stimulation(P < 0.05). At 1 min and 60 min, the amplitudes of the low-, medium-, and high-dose groups were lower than those of the control group(P < 0.05), the amplitudes of the medium-and highdose groups were lower than those of the low-dose group(P < 0.05), and the amplitude of the high-dose group was lower than that of the medium-dose group(P < 0.05). At 30 min, the amplitudes of the low-, medium-, and high-dose groups were lower than that of the control group(P < 0.05), and the amplitudes of the medium-and high-dose groups were lower than that of the low-dose group(P < 0.05). The Western blotting results showed that the relative expression levels of PSD95 of the low-, medium-, and high-dose groups were

关 键 词：亚慢性 铝 长时程增强 突触后致密蛋白95 棕榈酰化 

分 类 号：R114[医药卫生—卫生毒理学]