【摘要】 目的研究糖尿病大鼠并发阿尔茨海默病的可能机制以及氯化锂(LiCl)的作用。方法用链脲佐菌素(STZ)建立糖尿病大鼠模型,用32P放射性标记法检测对照组、糖尿病(DM)组、DM+NaCl组和DM+LiCl组的糖原合酶激酶-3(GSK-3)的活性,用蛋白印迹法检测tau蛋白磷酸化水平,用电跳台试验检测大鼠的保留记忆。结果DM组与对照组相比,GSK-3活性明显增加,tau蛋白磷酸化程度明显升高,且伴有记忆障碍(P<0·05)。与DM组相比较,DM+LiCl组GSK-3活性和tau蛋白过度磷酸化程度均降低(P<0·05,P<0·01),记忆障碍改善(P<0·05)。结论糖尿病大鼠脑皮层GSK-3活性升高,LiCl通过抑制GSK-3活性,降低tau蛋白过度磷酸化,改善糖尿病大鼠的记忆障碍。更多还原

【Abstract】 Objective To explore the mechanism of tau hyperphosphorylation and the effect of LiCl on tau phosphorylation and the memory retention deficits in streptozotocin-induced diabetes mellitus (DM) rats. Methods The rats were randomly divided into control,DM,DM+NaCl,and DM+LiCl groups and diabetes was induced by streptozotocin. The activity of glycogen synthase kinase-3 (GSK-3) was measured by ~ 32 P-labelling. The level of tau phosphorylated and changes of memory retention were examined by Western blotting and step down test,respectively. Results Compared with control group,the activity of GSK-3 and tau phosphorylation was increased,and the memory retention was impaired in DM group. When the rats were treated with LiCl,the activity of GSK-3 and hyperphosphorylation of tau were significantly arrested (P<0.05,P<0.01),and the memory retention deficit was significantly improved (P<0.05). Conclusion The hyperphosphorylation of tau can be induced by activation of GSK-3 in diabetic rats. Lithium protects tau from hyperphosphorylation and may rescue memory retention in the rats by inhibiting GSK-3 activity.更多还原