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。
Abstract
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 32P-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.
关键词
糖尿病 /
氯化锂 /
糖原合酶激酶-3 /
tau蛋白
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Key words
diabetes /
licl /
clycocen syntdase kinase -3 /
tau protein
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参考文献
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