钨酸锂抑制β淀粉样蛋白分泌及神经元的保护作用研究临床医学.docVIP

钨酸锂抑制β淀粉样蛋白分泌及神经元的保护作用研究临床医学 目录 TOC \o 1-9 \h \z \u 目录 1 正文 1 文1：钨酸锂抑制β淀粉样蛋白分泌及神经元的保护作用研究临床医学 1 1 材料与方法 3 2 结果 5 3 讨论 6 文2：单涎酸神经节苷脂对大鼠大脑中动脉缺血再灌注损伤的保护作用研究临床医学 7 1 材料与方法 9 2 结果 11 3 讨论 12 参考文摘引言： 14 原创性声明（模板） 16 文章致谢（模板） 16 正文 钨酸锂抑制β淀粉样蛋白分泌及神经元的保护作用研究临床医学 文1：钨酸锂抑制β淀粉样蛋白分泌及神经元的保护作用研究临床医学 【Abstract】 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 neuro 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 neuro from cerebral cortex of newborn mouse were cultured in B27supplemented neurobasal, a new serumfree medium combination, and identified by E staining; MTT assay was carried out to investigate the effect of the LT on development of neuro. Results ①Different concentratio of LT had no influence on the survival of M146L cells；② Different concentratio of LT could inhibit the secretion of Aβ142 by M146L cells；③Most of the neuro were stained to be positive with E, which suggested them being neuro; ④The results showed that LT ( mmol/L, or mmol/L) could increase the number and the length of neurites as well as the number of survival neuro. Conclusio Adequate LT could inhibit the secretion of Aβ142 by M146L cells and has a neuroprotective effect on the neuro from cerebral cortex of newborn mouse. 【Key words】 Lithium tungstate; Alzheimer′s disease; Amyloid betaprotein; M146L cells; Neuroprotective effect β淀粉样蛋白（Aβ142）生成抑制剂是目前阿尔茨海默病（AD）药物研发的重要方向，这类药物大多仍处于实验研究阶段，个别进入临床研究。近年研究表明，氯化锂具有神经保护作用，可拮抗多种因素诱导的神经元凋亡，在一定程度上促进神经元发生〔1〕。Phiel等研究发现氯化锂可通过抑制GSK3α而减少Aβ分泌〔2〕。同时，有研究发现钨酸钠亦是一种GSK3抑制剂〔3〕，并且与氯化锂合用具有协同作用〔4〕。因此，作者设想将氯化锂和钨酸钠经化学方法合成钨酸锂，其作用可能更优。本实验通过钨酸锂与前几种试剂对神经元作用的对比来验证这一假说，并探寻一种更佳的Aβ142生成抑制剂。钨酸锂为本实验室首次合成，也是国内外首次探讨钨酸锂对Aβ表达的影响，具有自主知识产权（专利号： 1 材料与方法 材料 实验动物 昆明种小鼠（广东省实验动物实验中心提供，合格证号：2003