β淀粉样肽结合乙醇脱氢酶及胆碱乙酰转移酶在糖尿病小鼠海马内表达的时程变化

doi:10.3969/j.issn.1006-7795.2013.01.010

首都医科大学学报 ›› 2013, Vol. 34 ›› Issue (1): 53-57.doi: 10.3969/j.issn.1006-7795.2013.01.010

• 神经系统疾病的基础研究 • 上一篇下一篇

β淀粉样肽结合乙醇脱氢酶及胆碱乙酰转移酶在糖尿病小鼠海马内表达的时程变化

闫颖, 李森, 赵志炜, 赵咏梅

首都医科大学宣武医院中心实验室神经变性病教育部重点实验室北京市老年病医疗研究中心, 北京 100053

收稿日期:2012-10-09 出版日期:2013-02-21 发布日期:2013-02-25
通讯作者: 赵咏梅 E-mail:yongmeizhao@hotmail.com
基金资助:
北京市自然科学基金(7122036);省部共建国家重点实验室培育基地脑重大疾病实验室开放课题(2012NZDJ03)资助。

Time course changes of amyloid-β peptide-binding alcohol dehydrogenase and choline acetyl transferase in hippocampus of diabetic mice

YAN Ying, LI Sen, ZHAO Zhiwei, ZHAO Yongmei

Central Laboratory, Xuanwu Hospital, Capital Medical University, Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing Geriatric Medical Research Center, Beijing 100053, China

Received:2012-10-09 Online:2013-02-21 Published:2013-02-25
Supported by:
This study was supported by Natural Science Foundation of Beijing (7122036);Public Foundation of Beijing Brain Diseases Key Laboratory(2012NZDJ03).

摘要/Abstract

摘要：

目的本研究通过观察β淀粉样肽结合乙醇脱氢酶(amyloid-β peptide-binding alcohol dehydrogenase, ABAD)及胆碱乙酰转移酶(choline acetyl transferase, ChAT)在糖尿病(diabetes mellitus, DM)小鼠海马CA1区表达的时程变化,探讨DM脑病发病的相关机制。方法 48只雄性昆明小鼠采用数字表法随机分为对照组(control, C, n=24)和DM组(n=24)。小鼠禁食12 h后,按200 mg/kg腹腔注射新鲜配制的链脲佐菌素(streptozocin, STZ),3 d后尾部测非禁食血糖,大于15 mmol/L者为DM模型复制成功。分别在造模后1周、4周及8周应用免疫组织化学染色方法观察C组与DM组小鼠海马CA1区ABAD及ChAT阳性细胞的变化。结果 1)ABAD免疫组织化学染色结果显示,C组小鼠海马CA1区ABAD阳性细胞数量少,染色浅;而造模后1周、4周、8周, DM组小鼠海马CA1区ABAD阳性细胞数量较C组增多,染色深。细胞计数结果显示,1周、4周及8周,DM组小鼠海马CA1区ABAD阳性细胞数量(18.50±2.72,21.10±2.47,18.90±2.08)比C组(14.30±2.63, 15.30±3.13, 14.10±3.07)明显增加,差异有统计学意义(P<0.01)。2)ChAT免疫组织化学染色结果显示,C组小鼠海马CA1区ChAT阳性细胞数量多,染色深;而造模后1周、4周及8周,DM组小鼠海马CA1区ChAT阳性细胞数较C组减少,染色变浅。细胞计数结果显示,1周、4周及8周DM组小鼠海马CA1区ChAT阳性细胞数量(21.20±2.15,19.60±3.50, 21.30±3.20)比C组(25.50±3.63, 26.40±3.37, 26.30±4.88)明显减少,差异有统计学意义(P<0.01)。结论 DM早期(1周)小鼠海马内即出现ABAD 表达增加,并持续至实验终点(8周),同时DM小鼠海马内ChAT表达明显减少。ABAD可能参与DM小鼠胆碱能神经元的变性过程,在DM脑病的发病机制中具有重要作用。

关键词: 糖尿病, 海马, &beta, 淀粉样肽结合乙醇脱氢酶, 胆碱乙酰转移酶

Abstract:

Objective To observe the time course changes of expression of amyloid-β peptide-binding alcohol dehydrogenase (ABAD) and choline acetyl transferase (ChAT) in the hippocampal CA1 region of diabetic mice, in order to explore the mechanism of diabetic encephalopathy.Methods Forty-eight male mice were divided into a control (C) group (n=24) and a diabetes mellitus (DM) group (n=24) randomly. Streptozocin (STZ) was freshly prepared and injected at 200 mg/kg, i.p. into mice which had been fasted for 12 h. Three days later, blood glucose in a tail-vein sample was determined; a value ≥15 mmol/L was accepted as a successful induction of a diabetic model. The expression changes of ABAD and ChAT in the hippocampus of group C and DM group mice at 1 week, 4 weeks and 8 weeks after DM models establishment were studied by immunohistochemical staining. Results 1) The result of ABAD immunohistochemical staining showed that there were slightly stained ABAD-positive cells in hippocampal CA1 region of group C mice,while more darkly stained ABAD-positive cells in hippocampal CA1 region were found in DM group mice at 1 week, 4 weeks and 8 weeks. The numbers of ABAD-positive cells in the hippocampal CA1 region of DM group mice at 1 week, 4 weeks and 8 weeks (18.50±2.72,21.10±2.47,18.90±2.08) increased significantly (P<0.01) compared with those of group C mice (14.30±2.63, 15.30±3.13, 14.10±3.07). 2) The ChAT immunohistochemical staining showed that there were some darkly stained ChAT-positive cells in hippocampal CA1 region of group C mice,while DM group mice at 1 week, 4 weeks and 8 weeks had less ChAT-positive cells in hippocampal CA1 region compared with those of group C, the staining was pale. The numbers of ChAT-positive cells in the hippocampal CA1 region of DM group mice at 1 week, 4 weeks and 8 weeks (21.20±2.15,19.60±3.50,21.30±3.20) decreased significantly (P<0.01) compared with those of group C mice(25.50±3.63, 26.40±3.37, 26.30±4.88).Conclusion The expression of ABAD in hippocampus of DM mice increased compared with that of normal control mice at early stage of DM (1 week) and sustained till the end of this study (DM 8 weeks). Meanwhile, the expression of ChAT cells in hippocampus of DM mice decreased significantly. ABAD might be involved in the degeneration of cholinergic neuron in DM mice and play important role in the pathogenesis of diabetic encephalopathy.

Key words: diabetes mellitus, hippocampus, amyloid-&beta, peptide-binding alcohol dehydrogenase, choline acetyl transferase

中图分类号:

R587.1

闫颖, 李森, 赵志炜, 赵咏梅. β淀粉样肽结合乙醇脱氢酶及胆碱乙酰转移酶在糖尿病小鼠海马内表达的时程变化[J]. 首都医科大学学报, 2013, 34(1): 53-57.

YAN Ying, LI Sen, ZHAO Zhiwei, ZHAO Yongmei. Time course changes of amyloid-β peptide-binding alcohol dehydrogenase and choline acetyl transferase in hippocampus of diabetic mice[J]. Journal of Capital Medical University, 2013, 34(1): 53-57.

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β淀粉样肽结合乙醇脱氢酶及胆碱乙酰转移酶在糖尿病小鼠海马内表达的时程变化

Time course changes of amyloid-β peptide-binding alcohol dehydrogenase and choline acetyl transferase in hippocampus of diabetic mice

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