長期口服阿卡波糖對老年SAMP8小鼠空間學(xué)習(xí)和記憶能力損害的保護(hù)作用
發(fā)布時間：2018-11-24 10:30
【摘要】：背景年齡相關(guān)記憶損害(Age-associated memory impairment,AAMI)不僅能夠降低老年人的生活質(zhì)量,而且能夠增加社會的醫(yī)療支出,積極探索能夠緩解AAMI的方法具有重要意義。葡萄糖代謝和胰島素/胰島素樣生長因子-1(insulin-like growth factor 1,IGF-1)信號通路與認(rèn)知功能相關(guān)。葡萄糖和胰島素/IGF-1信號系統(tǒng)受損時,能夠降低認(rèn)知功能。提高葡萄糖代謝和胰島素/IGF-1信號系統(tǒng)的活性,有助于改善認(rèn)知功能。阿卡波糖是一種a-葡萄糖甘酶抑制劑,不僅能夠調(diào)節(jié)血糖和胰島素/IGF-1信號通路,還能夠延緩年齡相關(guān)性疾病如心腦血管疾病等的發(fā)生和發(fā)展。因此,我們推測長期口服阿卡波糖可能能夠緩解AAMI。乙�；腍3K9(acetylated histone H3 lysine 9,H3K9ac)和H4K8(acetylated histone H4 lysine 8,H4K8ac)是組蛋白乙�；揎椫醒芯枯^多的對象,與認(rèn)知功能有關(guān)。但是,H3K9ac和H4K8ac是否與阿卡波糖和AAMI相關(guān)則未見報(bào)道。目的探討1)長期口服阿卡波糖對AAMI的抑制效應(yīng);2)血糖、胰島素/IGF-1信號系統(tǒng)以及H3K9ac和H4K8ac與阿卡波糖作用的相關(guān)性。方法3月齡的SAMP8小鼠隨機(jī)分為阿卡波糖組(雌鼠5只,雄鼠4只)和老年空白對照組(雌鼠4只,雄鼠4只),阿卡波糖組小鼠從3月齡開始每日飲用含有阿卡波糖的自來水(20 mg/kg/d),直至9月齡進(jìn)行行為學(xué)實(shí)驗(yàn)前停止,對照組小鼠只飲用普通的自來水。另加入一組3月齡的小鼠作為青年空白對照組(雌鼠6只,雄鼠5只),與阿卡波糖組和老年對照組小鼠一起進(jìn)行實(shí)驗(yàn)。Morris水迷宮實(shí)驗(yàn)用于檢測小鼠的空間學(xué)習(xí)和記憶能力,酶聯(lián)免疫吸附試驗(yàn)和免疫組織化學(xué)染色方法分別用于檢測小鼠的血清學(xué)指標(biāo)和背海馬的蛋白含量。結(jié)果與青年對照組小鼠相比,老年對照組小鼠的空間學(xué)習(xí)和記憶能力以及血清胰島素濃度、背海馬胰島素受體(insulin receptors,Ins Rs)、H3K9ac和H4K8ac的相對含量均降低。有趣的是,阿卡波糖組小鼠較老年對照組小鼠,空間學(xué)習(xí)和記憶能力以及血清胰島素濃度、Ins Rs、H3K9ac和H4K8ac的相對含量均升高。小鼠的空間學(xué)習(xí)和記憶能力的提高與血清胰島素濃度、Ins Rs、H3K9ac和H4K8ac的相對含量的提高呈明顯的正相關(guān)關(guān)系。結(jié)論長期口服阿卡波糖能夠改善SAMP8小鼠的年齡相關(guān)性空間學(xué)習(xí)和記憶能力的減退,與緩解胰島素系統(tǒng)、H3K9ac和H4K8ac的年齡相關(guān)性降低改變有關(guān)。
[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.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R749.16
本文編號：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.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R749.16
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 賈敏;劉文學(xué);楊嬌嬌;紀(jì)木火;段滿林;楊建軍;徐建國;;術(shù)后認(rèn)知功能障礙老年小鼠海馬內(nèi)組蛋白乙�；康淖兓痆J];臨床麻醉學(xué)雜志;2014年10期
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