α-硫辛酸对铅暴露海马神经元突触生成的影响和保护机制  

Protective Effect of Alpha Lipoic Acid on Lead-induced Synaptic Damage in Rat Hippocampus

作　　者：葛梦梦 汪惠丽[1] 刘志华[1] 胡繁[1] 吴春艳[1] 

机构地区：[1]合肥工业大学生物与食品工程学院,安徽合肥230009

出　　处：《安徽农业科学》2015年第5期105-108,221,共5页Journal of Anhui Agricultural Sciences

基　　金：国家自然基金(31200851);国家科技部973项目(2012-CB525003)

摘　　要：[目的]探讨α-硫辛酸对铅暴露大鼠海马神经元树突棘突触形成的神经保护作用和机制。[方法]取新生大鼠(出生后24 h内,P0)海马组织进行细胞培养,体外培养第6天(DIV6)转染绿色荧光蛋白(GFP),DIV7开始加入醋酸铅(1μmol/L)处理至试验结束(DIV13),并在DIV12给予α-硫辛酸(100 nmol/L,1μmol/L和10μmol/L)处理24 h,然后观察树突棘的变化并进行量化分析。整体动物试验以SD母鼠喂饲300 mg/L醋酸铅水溶液,幼鼠自出生后至断奶(出生后第21天)经母乳铅暴露。幼鼠自从出生后第14天(PND14)到PND21经腹腔注射给药25 mg/kgα-硫辛酸,研究LA对铅暴露的海马神经元海马树突棘的修复作用,检测海马AMPA和NMDA受体的表达水平。[结果]α-硫辛酸对铅处理的体外培养海马神经元树突棘密度损伤有保护作用,且呈剂量依赖性。整体动物试验发现,铅暴露能显著降低海马CA1区锥体神经元和DG区颗粒细胞的树突棘密度。α-硫辛酸可以显著上调突触后NMDA受体亚单位NR2B的表达(P<0.05),但不影响AMPA受体亚单位的合成和表达。[结论]α-硫辛酸可以修复铅暴露引起的突触损伤,富含α-硫辛酸的食品可防治儿童铅中毒。[ Objective ] To investigate the protective effect of alpha lipoic acid on the spine formation and maturation against lead-induced impairments. [ Method ] Primary hippocampal cultures were prepared from brain of new postnatal SD rats （P0）. Hippocampa] cultures were lentiviral infected with GFP at DIV 6, at DIV 12 after 5 clays Pb^2＋ exposure （ 1 μmol/L） with 24 hours LA treatment （ 100 nmol/L, 1 μmol/L and 10 μmol/L） then observe the changes of dendritic spines. Spraguc-Dawley （SD） female rats were feed on 300 mg/L lead acetate solu- tion, on parturition day, the pups acquired lead through breast milk from parturition to weaning. From PND14-21, the offspring were injected intraperitoneally （ip） daily with LA 25 mg/kg. [ Result] Lead exposure can significantly reduce the density of the dendritic spines of neurons in vitro, the dendritic spines significantly increased with the different concentration of LA. The animal experiment study found that lead expo- sure can significantly decrease the dendritic spine density of CA1 pyramidal and DG granule neurons in hippocampus. Research shows that the mechanism of alpha lipoic acid, LA can significantly increase the postsynaptic NMDA receptor subunit NR2B expression （ P 〈 0.05 ）, but does not affect the synthesis and expression of AMPA receptor subunits. Protective effect of alpha lipoic acid on lead-induced synaptic damage in rat hippocampus was studied. The expression level of AMPA and NMDA receptor was detected. [ Conclusion] Alpha lipoic acid can repair the synaptic function of lead induced neurotoxicity, and the foods rich in alpha lipoic acid can prevent children lead poisoning.

关 键 词：铅 Α-硫辛酸 海马 树突棘 NMDAR-2B 

分 类 号：S859.791[农业科学—临床兽医学]