长期口服阿卡波糖对老年SAMP8小鼠空间学习和记忆能力损害的保护作用
发布时间：2018-11-24 10:30
【摘要】：背景年龄相关记忆损害(Age-associated memory impairment,AAMI)不仅能够降低老年人的生活质量,而且能够增加社会的医疗支出,积极探索能够缓解AAMI的方法具有重要意义。葡萄糖代谢和胰岛素/胰岛素样生长因子-1(insulin-like growth factor 1,IGF-1)信号通路与认知功能相关。葡萄糖和胰岛素/IGF-1信号系统受损时,能够降低认知功能。提高葡萄糖代谢和胰岛素/IGF-1信号系统的活性,有助于改善认知功能。阿卡波糖是一种a-葡萄糖甘酶抑制剂,不仅能够调节血糖和胰岛素/IGF-1信号通路,还能够延缓年龄相关性疾病如心脑血管疾病等的发生和发展。因此,我们推测长期口服阿卡波糖可能能够缓解AAMI。乙酰化的H3K9(acetylated histone H3 lysine 9,H3K9ac)和H4K8(acetylated histone H4 lysine 8,H4K8ac)是组蛋白乙酰化修饰中研究较多的对象,与认知功能有关。但是,H3K9ac和H4K8ac是否与阿卡波糖和AAMI相关则未见报道。目的探讨1)长期口服阿卡波糖对AAMI的抑制效应;2)血糖、胰岛素/IGF-1信号系统以及H3K9ac和H4K8ac与阿卡波糖作用的相关性。方法3月龄的SAMP8小鼠随机分为阿卡波糖组(雌鼠5只,雄鼠4只)和老年空白对照组(雌鼠4只,雄鼠4只),阿卡波糖组小鼠从3月龄开始每日饮用含有阿卡波糖的自来水(20 mg/kg/d),直至9月龄进行行为学实验前停止,对照组小鼠只饮用普通的自来水。另加入一组3月龄的小鼠作为青年空白对照组(雌鼠6只,雄鼠5只),与阿卡波糖组和老年对照组小鼠一起进行实验。Morris水迷宫实验用于检测小鼠的空间学习和记忆能力,酶联免疫吸附试验和免疫组织化学染色方法分别用于检测小鼠的血清学指标和背海马的蛋白含量。结果与青年对照组小鼠相比,老年对照组小鼠的空间学习和记忆能力以及血清胰岛素浓度、背海马胰岛素受体(insulin receptors,Ins Rs)、H3K9ac和H4K8ac的相对含量均降低。有趣的是,阿卡波糖组小鼠较老年对照组小鼠,空间学习和记忆能力以及血清胰岛素浓度、Ins Rs、H3K9ac和H4K8ac的相对含量均升高。小鼠的空间学习和记忆能力的提高与血清胰岛素浓度、Ins Rs、H3K9ac和H4K8ac的相对含量的提高呈明显的正相关关系。结论长期口服阿卡波糖能够改善SAMP8小鼠的年龄相关性空间学习和记忆能力的减退,与缓解胰岛素系统、H3K9ac和H4K8ac的年龄相关性降低改变有关。
[Abstract]:Background Age-related memory impairment (Age-associated memory impairment,AAMI) can not only reduce the quality of life of the elderly, but also increase the social medical expenditure. It is of great significance to explore ways to alleviate AAMI. Glucose metabolism and insulin / insulin-like growth factor-1 (insulin-like growth factor 1) signaling pathway are associated with cognitive function. When glucose and insulin / IGF-1 signaling systems are impaired, cognitive function is reduced. Increasing glucose metabolism and the activity of insulin / IGF-1 signaling system can improve cognitive function. Acarbose is an a- glucosaminase inhibitor, which can not only regulate blood glucose and insulin / IGF-1 signaling pathway, but also delay the onset and development of age-related diseases such as cardiovascular and cerebrovascular diseases. Therefore, we speculate that long-term oral acarbose may alleviate AAMI.. Acetylated H3K9 (acetylated histone H3 lysine 9 (H3K9ac) and H4K8 (acetylated histone H4 lysine 8 (H4K8ac) are the subjects of histone acetylation modification, which are related to cognitive function. However, whether H3K9ac and H4K8ac are associated with acarbose and AAMI has not been reported. Objective to investigate the inhibitory effect of long-term oral acarbose on AAMI, and to investigate the correlation of glucose, insulin / IGF-1 signaling system and H3K9ac and H4K8ac with acarbose. Methods SAMP8 mice aged 3 months were randomly divided into acarbose group (5 female and male 4) and aged blank control group (4 female and 4 male). The mice in the acarbose group drank tap water containing acarbose daily (20 mg/kg/d) from the age of 3 months until the end of the behavioral experiment at 9 months. The control group only drank the normal tap water. In addition, a group of 3-month-old mice was added as the control group (6 female and 5 male) as the control group. The experiment was carried out together with the acarbose group and the aged control group. The Morris water maze test was used to test the spatial learning and memory ability of the mice. Enzyme linked immunosorbent assay (Elisa) and immunohistochemical staining were used to detect the serological indexes and protein content in the dorsal hippocampus of mice. Results compared with the young control group, the spatial learning and memory ability, the serum insulin concentration and the relative content of insulin receptors,Ins Rs), H3K9ac and H4K8ac were decreased in the aged control group. Interestingly, the ability of spatial learning and memory, serum insulin concentration, relative content of Ins Rs,H3K9ac and H4K8ac in the acarbose group were higher than those in the aged control group. There was a significant positive correlation between the improvement of spatial learning and memory ability and the increase of serum insulin concentration, the relative content of Ins Rs,H3K9ac and H4K8ac in mice. Conclusion Long-term oral acarbose can improve the age-related spatial learning and memory of SAMP8 mice, which is related to the remission of insulin system, the decrease of age-related changes of H3K9ac and H4K8ac.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R749.16
本文编号：2353353
[Abstract]:Background Age-related memory impairment (Age-associated memory impairment,AAMI) can not only reduce the quality of life of the elderly, but also increase the social medical expenditure. It is of great significance to explore ways to alleviate AAMI. Glucose metabolism and insulin / insulin-like growth factor-1 (insulin-like growth factor 1) signaling pathway are associated with cognitive function. When glucose and insulin / IGF-1 signaling systems are impaired, cognitive function is reduced. Increasing glucose metabolism and the activity of insulin / IGF-1 signaling system can improve cognitive function. Acarbose is an a- glucosaminase inhibitor, which can not only regulate blood glucose and insulin / IGF-1 signaling pathway, but also delay the onset and development of age-related diseases such as cardiovascular and cerebrovascular diseases. Therefore, we speculate that long-term oral acarbose may alleviate AAMI.. Acetylated H3K9 (acetylated histone H3 lysine 9 (H3K9ac) and H4K8 (acetylated histone H4 lysine 8 (H4K8ac) are the subjects of histone acetylation modification, which are related to cognitive function. However, whether H3K9ac and H4K8ac are associated with acarbose and AAMI has not been reported. Objective to investigate the inhibitory effect of long-term oral acarbose on AAMI, and to investigate the correlation of glucose, insulin / IGF-1 signaling system and H3K9ac and H4K8ac with acarbose. Methods SAMP8 mice aged 3 months were randomly divided into acarbose group (5 female and male 4) and aged blank control group (4 female and 4 male). The mice in the acarbose group drank tap water containing acarbose daily (20 mg/kg/d) from the age of 3 months until the end of the behavioral experiment at 9 months. The control group only drank the normal tap water. In addition, a group of 3-month-old mice was added as the control group (6 female and 5 male) as the control group. The experiment was carried out together with the acarbose group and the aged control group. The Morris water maze test was used to test the spatial learning and memory ability of the mice. Enzyme linked immunosorbent assay (Elisa) and immunohistochemical staining were used to detect the serological indexes and protein content in the dorsal hippocampus of mice. Results compared with the young control group, the spatial learning and memory ability, the serum insulin concentration and the relative content of insulin receptors,Ins Rs), H3K9ac and H4K8ac were decreased in the aged control group. Interestingly, the ability of spatial learning and memory, serum insulin concentration, relative content of Ins Rs,H3K9ac and H4K8ac in the acarbose group were higher than those in the aged control group. There was a significant positive correlation between the improvement of spatial learning and memory ability and the increase of serum insulin concentration, the relative content of Ins Rs,H3K9ac and H4K8ac in mice. Conclusion Long-term oral acarbose can improve the age-related spatial learning and memory of SAMP8 mice, which is related to the remission of insulin system, the decrease of age-related changes of H3K9ac and H4K8ac.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R749.16
【参考文献】
相关期刊论文 前1条
1 贾敏;刘文学;杨娇娇;纪木火;段满林;杨建军;徐建国;;术后认知功能障碍老年小鼠海马内组蛋白乙酰化含量的变化[J];临床麻醉学杂志;2014年10期
，本文编号：2353353
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