罗格列酮改善链脲霉素诱导的糖尿病小鼠认知障碍及机制研究

摘要/Abstract

摘要： 目的：研究罗格列酮（rosiglitazone）对链脲霉素诱导的 1 型糖尿病小鼠认知功能的影响及其作用机制。方法：单剂量尾静脉注射（iv）链脲霉素（150 mg• kg^-1）诱导小鼠 1 型糖尿病模型，将造模成功（空腹血糖>11.1 mmol• L^-1）的小鼠随机分为3 组：模型组，罗格列酮 3.2,1.6 mg• kg^-1• d^-1 剂量组；另设正常对照组，每组 10～12只，连续灌胃（ig）给药 6 周。第 6 周采用 Morris 水迷宫和 Y 迷宫实验评价认知功能，并检测空腹血糖、血清胰岛素、海马和皮层区 Aβ₄₀ ,Aβ₄₂糖尿病动物脑内β分泌酶（β-site amyloid precursor protein cleaving enzyme,BACE1）含量。结果：与模型组相比，罗格列酮 3.2 mg• kg^-1 剂量组能显著缩短糖尿病小鼠定位航行试验的潜伏期（P<0.05），增加空间探索实验中平台所在象限的停留时间百分率（P<0.05），并增加糖尿病小鼠在 Y 迷宫测试中的正确反应次数（P<0.05）；罗格列酮对 1 型糖尿病小鼠空腹血糖和胰岛素水平无显著影响；罗格列酮 3.2 mg• kg^-1 剂量显著降低糖尿病小鼠脑内海马和皮层区 Aβ₄₀（P<0.05,P<0.05）和 Aβ₄₂（P<0.05,P<0.05）的水平而对海马和皮层区 BACE1 水平无显著影响。结论：罗格列酮 3.2 mg• kg^-1 剂量可通过降低脑内 Aβ水平而改善 1 型糖尿病小鼠认知障碍。

关键词: 糖尿病, 认知障碍, 罗格列酮, &, beta, 淀粉样蛋白

Abstract: Objective: To investigate the effects of rosiglitazone on cognitive function in streptozotocin-induced diabetic mice and the underlying mechanisms. Methods: Diabetic mice induced by a single intravenous injection of streptozotocin（150 mg• kg^-1 body weigh）were used as animal model of type 1 diabetes. Diabetic mice with hyperglycemia（>11.1 mmol•L^-1）were randomly divided into three groups,including untreated diabetes group, rosiglitazone( 3.2 mg•kg^-1 and 1.6 mg•kg^-1)treated groups（10~12 mice/group）. After orally administration of rosiglitazone for 6 w, rosiglitazone-treated diabetic mice, untreated diabetic mice and non-diabetic controls were tested in the Morris water maze and Y maze. The serum insulin，the levels of Aβ₄₀，Aβ₄₂ and BACE1 in hippocampus and cortex were determined by ELISA assays，and the blood glucose was measured by the glucose oxidase method. Results: Both water maze and Y maze learning were impaired in diabetic mice. In Morris water maze, rosiglitazone（3.2 mg• kg^-1）significantly decreased the escape latency（P<0.05）and increased the time spent in the platform quadran（P<0.05）compared with the vehicle diabetic group. Rosiglitazone（3.2 mg• kg^-1）also significantly increased the number of correct（P<0.05）in Y maze test. Rosiglitazone treatment did not decrease the blood glucose and serum insulin of diabetic mice. Rosiglitazone（3.2 mg• kg^-1）significantly decreased the Aβ₄₀（P<0.05, P<0.05）and Aβ₄₂（P<0.05, P<0.05）levels in both hippocampus and cerebral cortex of diabetic mice, without reducing the increased BACE1 level. Conclusion: Rosiglitazone at the dosage of 3.2 mg• kg^-1improves cognitive impairments in streptozotocin-induced diabetic mice via the alleviation of the Aβ burden in the brain.

Key words: diabetes mellitus, cognitive impairment, rosiglitazone, &, beta, -amyloid protein（A&, beta, ）

中图分类号:

R971

张亭亭，刘丽萍，姜荔莹，胡伟，龙燕，洪浩. 罗格列酮改善链脲霉素诱导的糖尿病小鼠认知障碍及机制研究[J]. 神经药理学报, 2011, 1(2): 1-6.

ZHANG Ting-ting，LIU Li-ping，JIANG Li-ying，HU Wei，LONG Yan，HONG Hao. Rosiglitazone Improves Cognitive Impairment in Streptozotocin-induced Diabetic Mice and its Mechanisms[J]. Acta Neuropharmacologica, 2011, 1(2): 1-6.

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