糖尿病模型大鼠认知功能障碍及海马N-甲基-D-天冬氨酸受体表达变化

Cognitive dysfunction and N-Methyl-D-Aspartate receptor expression in streptozotocin-diabetic rats

目的:探讨糖尿病模型大鼠是否出现认知功能障碍以及与海马N-甲基-D-天冬氨酸(NMDA)受体的关系。方法:SD大鼠随机分为正常组及糖尿病组。糖尿病组运用链脲佐菌素(STZ,55mg/kg)腹腔注射建立STZ大鼠模型。两组通过Y型迷宫测试其学习记忆能力,并采用Westernblot免疫印迹检测两组大鼠海马NMDA受体NR2B亚基的蛋白表达水平。结果:(1)糖尿病组血糖较正常组血糖明显升高[(31.1±2.3)mmol/Lvs(4.8±0.6)mmol/L,P<0.01],而糖尿病组大鼠体质量在12周后较正常组明显减轻[(167.75±12.1)gvs(325.70±34.6)g,P<0.01]。(2)Y型迷宫试验中,糖尿病组的大鼠出现的错误反应次数明显高于正常组(P<0.001)。并且正常组达标所需时间为(3.50±0.53)d,而糖尿病组大鼠在训练的第5天仍旧不能达标。(3)糖尿病组海马NMDA受体NR2B亚基的蛋白表达减弱,与正常组比较差异有显著性(1.255±0.094vs2.606±0.090,P<0.01)。结论:糖尿病大鼠可出现明显的学习记忆等认知功能的减退,海马NMDA受体NR2B亚基的蛋白表达下降可能是糖尿病脑病的重要机制之一。

Objective To explore the mechanism of cognitive dysfunction in streptozotocin-diabetic rats. Methods Male Sprague-Dawley rats were randomized to model group or control group. The rat model of diabetes mellitus was established by an intraperitoneal injection of streptozotocin （55 mg/kg）. The learning and memory ability of the rats in two groups was detected by Y-maze test. The expression of N-Methyl-D-Aspartate （NMDA） receptor NR2B subunit in rat hippocampus was determined by Western blot. Results Blood glucose level was markedly higher in the model group than that in the control group [（31.1 ± 2.3）mmol/L vs （4.8 ± 0.6）mmol/L, P〈0.01], while body mass was lower on week 12 [（167.75 ± 12.1）g vs （325.70 ± 34.6）g, P〈0.01]. Error times in the model group was significantly higher than that in the control group in Y-maze test （P〈0.001）. The number of days the rats in the control group needed to complete Y-type maze was （3.50 ± 0.53）d, but those in the model group did not complete Y-type maze within 5 days. The expression of NMDA receptor NR2B subunit was significantly lower in the model group than in the control group （1.255 ± 0.094 vs 2.606 ± 0.090, P〈0.01）. Conclusions Streptozotocin-diabetic rats may develop a marked decrease in learning and memory ability. The reduced expression of NMDA receptor NR2B subunit may be one of the important mechanisms of diabetic encephalopathy.