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。
Objective To explore the mechanism of tau hyperphosphorylation and the effect of LiCI 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 diabees 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 tan 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.
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2006年第2期244-248,共5页
Acta Academiae Medicinae Sinicae
基金
国家自然科学基金(30430270
30472030
30400068)~~
