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 |
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引用本文: | 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].张家口医学院学报,2011(2):1-6. |
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作者姓名: | 张亭亭 刘丽萍 姜荔莹 胡伟 龙燕 洪浩 |
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作者单位: | [1]中国药科大学药理教研室,中国南京 210009 [2]安徽医科大学第二附属医院药剂科,中国合肥 230001 |
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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。
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关 键 词: | 糖尿病 认知障碍 罗格列酮 β淀粉样蛋白 |
Rosiglitazone Improves Cognitive Impairment in Streptozotocin- induced Diabetic Mice and its Mechanisms |
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Authors: | ZHANG Ting-ting LIU Li-ping JIANG Li-ying HU Wei LONG Yan HONG Hao |
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Institution: | 1. Department of Pharmacology,China Pharmaceutical University,Nanjing,210009,China 2. Department of Pharmacy,Second Affiliated Hospital of Anhui Medical University,Hefei,230001 ,China |
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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 weight) 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·d^-1 and 1.6 mg·kg^-1·d^-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 quadrant(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-1 improves cognitive impairments in streptozotocin-induced diabetic mice via the alleviation of the Aβ burden in the brain. |
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Keywords: | diabetes mellitus cognitive impairment rosiglitazone β-amyloid protein(Aβ) |
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