钨酸锂抑制β-淀粉样蛋白分泌及神经元的保护作用研究  

Inhibitory effect of lithium tungstate on the secretion of amyloid beta-protein 1-42,and its neuroprotection

作　　者：侯军代[1] 路露[1] 张晓裕[1] 罗焕敏[2] 

机构地区：[1]暨南大学医学院药理学系,广东广州510632 [2]暨南大学-香港大学脑功能与健康联合实验室

出　　处：《中国老年学杂志》2009年第22期2877-2880,共4页Chinese Journal of Gerontology

摘　　要：目的研究钨酸锂对人淀粉样前体蛋白及早老素-1(M146L)细胞分泌β-淀粉样蛋白(Aβ1-42)的影响及其对体外培养新生小鼠大脑皮层神经元的保护作用。方法①体外培养转染AD相关基因、可分泌Aβ1-42的M146L细胞,在培养液中加入低、中、高剂量(3.1、5、8mmol/L)钨酸锂或阳性对照药,通过对M146L细胞活性及培养基中Aβ1-42含量的测定,研究钨酸锂对M146L细胞分泌Aβ1-42的影响。②体外无血清培养新生小鼠大脑皮层神经元,采用NSE免疫细胞化学染色法进行神经元鉴定;观察神经元突起生长状况,分析研究钨酸锂对大脑皮层神经元的神经保护作用。结果①低、中、高剂量钨酸锂对M146L均无细胞毒性;②低、中、高剂量钨酸锂可抑制M146L细胞分泌Aβ1-42;③原代培养的新生小鼠大脑皮层神经元,经NSE免疫细胞化学染色被染成棕褐色的细胞占绝大多数,表明所培养细胞基本为神经元;④除低浓度(0.008mmol/L)外,终浓度分别为0.2,0.04mmol/L的钨酸锂均能明显使突起数目和长度增加,可促进神经元的存活。结论适量的钨酸锂可抑制M146L细胞分泌Aβ1-42;对新生小鼠大脑皮层神经元具有神经保护作用。Objective To explore the effects of lithium tungstate（LT） on the secretion of amyloid beta-protein 1-42（Aβ1-42）of M146L and the neuropretection on neurons from cerebral cortex of newborn mouse in vitro.Methods ① M146L cells were culture by low,middle and high dose of LT or positive control drug and the cell activity and the content of Aβ1-42 were detected.② The neurons from cerebral cortex of newborn mouse were cultured in B27-supplemented neurobasal,a new serum-free medium combination,and identified by NSE staining;MTT assay was carried out to investigate the effect of the LT on development of neurons.Results ①Different concentrations of LT had no influence on the survival of M146L cells;② Different concentrations of LT could inhibit the secretion of Aβ1-42 by M146L cells;③Most of the neurons were stained to be positive with NSE,which suggested them being neurons;④The results showed that LT（0.04 mmol/L,or 0.2 mmol/L） could increase the number and the length of neurites as well as the number of survival neurons.Conclusions Adequate LT could inhibit the secretion of Aβ1-42 by M146L cells and has a neuroprotective effect on the neurons from cerebral cortex of newborn mouse.

关 键 词：钨酸锂 阿尔茨海默病 M146L细胞 Β-淀粉样蛋白 神经保护作用 

分 类 号：R96[医药卫生—药理学]