糖尿病大鼠糖原合酶激酶-3与记忆障碍的关系

Study on correlations of glycogen synthase kinase-3 and memory impairment in diabetic rat

目的探讨糖尿病大鼠皮质糖原合酶激酶-3（glycogen synthase kinase-3,GSK-3）的变化在记忆障碍中的作用。方法用链脲佐菌素（Streptozotoc in STZ）建立糖尿病大鼠模型,用32P放射性标记法检测对照组,DM（Diabetes mellitus）组,DM＋碳酸锂（Li2CO3）组GSK-3的活性,用蛋白印迹法检测磷酸化GSK-3β的表达,用电跳台试验检测大鼠的学习及记忆保留情况。结果与对照组（1.07±0.07）相比,DM组的GSK-3活性（1.38±0.08）明显升高（P〈0.01）,GSK-3βSer9位点的磷酸化水平（0.84±0.06）比对照组（1.05±0.08）明显降低（P〈0.01）,并且,犯错次数[（2.6±0.89）次/3min]比对照组[（1.20±0.84）次/3min]增加（P〈0.05）,潜伏期[（94.00±23.02）s/3min]也比对照组明显缩短[（144.00±20.74]s/3min]（P〈0.01）,应用Li2CO3干预后,GSK-3活性（1.13±0.06）明显降低（P〈0.01）,GSK-3βSer9位点的磷酸化水平（0.97±0.06）恢复（P〈0.01）,犯错次数[（1.40±0.55）次/3min]降低（P〈0.05）,潜伏期[（130.00±18.72）s/3min]明显延长（P〈0.05）。结论糖尿病大鼠脑皮质GSK-3活性升高,可能导致其学习及记忆障碍,Li2CO3抑制GSK-3后,明显改善糖尿病大鼠的学习及记忆障碍。

Objective To explore the role of glycogen synthase kinase-3 （GSK-3） in the formation of memory impairment in streptozotocin-induced diabetes mellitus （ DM ） rats. Methods The rats were divided randomly into control, DM, and DM ± Li2 CO3 groups, and diabetes was induced by streptozotocin. The activity of GSK-3 was measured by 32↑p-labelling. The level of phosphorylated GSK-3 β at Ser9 epitope was examined by Western blot, and changes of memory retention were measured by step-down test. Results Compared with control group（ 1.07 ± 0.07 ） , the activity of GSK-3 （ 1.38 ± 0.08 ） was increased（ P〈 0.01 ）. The level of phosphorylated GSK-3β at Ser9 epitope （0.84 ± 0.06 ） was also decreased （ P 〈 0.01 ）compared with control group（ 1.05 ± 0.08）. The memory retention was impaired in DM group： error times（2.6 ±0.89 times/3min） was increased（ P 〈 0.05 ） , and latency （ 94 ± 23.02 sec/3 min ） was shortened （ P 〈 0.01 ） compared with control group （ 1.2 ± 0.84 times/3min, 144 ±20.74 sec/3min）. When the DM rats were treated with Li2CO3 , the activity of GSK-3（ 1.13 ± 0.06） was arrested（ P 〈 0.01 ） , and the level of phosphorylated GSK-3[3 at Ser9 epitope （ 0.97 ± 0.06 ） was reversed （ P〈0. 01 ）. Moreover, the memory retention deficit was improved： error time（ 1.4 ± 0.55 times/3min） was decreased （ P 〈 0.05 ） , and the latency （ 130 ± 18.72 see/3 vain ） was prolonged （ P 〈 0.01 ）. Conclusion The memory impairment is induced by high activation of GSK-3 in diabetic rats, and is improved by inhibitions of GSK- 3 with Li2CO3 administration.