异常黏液质成熟剂对APP/PS1转基因阿尔茨海默病小鼠学习记忆和脑组织RAGE、LRP1蛋白表达的影响
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摘要
目的观察异常黏液质成熟剂对APP/PS1转基因阿尔茨海默病(AD)小鼠学习记忆和脑组织RAGE、LRP1蛋白表达的影响,探讨其作用机制。方法选取3月龄APP/PS1转基因AD模型小鼠并将其随机分为模型组、阳性药组和异常黏液质成熟剂高、中、低剂量组,每组18只,另取18只3月龄C57BL/6J小鼠作为正常组。各给药组给予相应药物灌胃,连续6个月。跳台实验观察小鼠学习和记忆能力;免疫组化和Western blot检测LRP1、RAGE蛋白表达。结果与正常组比较,模型组学习成绩反应期时间和错误次数增加,记忆成绩潜伏期时间减少、错误次数增加(P<0.01);与模型组比较,各给药组学习成绩反应期时间和错误次数减少,记忆成绩潜伏期时间增加、错误次数减少(P<0.05,P<0.01);免疫组化和Western blot结果显示,与正常组比较,模型组小鼠脑组织LRP1表达降低、RAGE表达增加(P<0.05);与模型组比较,异常黏液质成熟剂各剂量组小鼠脑组织LRP1表达增加、RAGE表达降低(P<0.05,P<0.01)。结论异常黏液质成熟剂可改善APP/PS1转基因AD小鼠空间学习记忆能力,调整RAGE和LRP1的表达。
Objective To investigate the effects of Abnormal Phlegmatic Munziq on ability of learning and memory, and protein expressions of brain tissue RAGE and LRP1 of APP/PS1 transgenetic mice model of AD; To discuss its mechanism of action. Methods Three-month-old APP/PS1 transgenic mice were randomly divided into 5 groups: model control group, positive control group, Abnormal Phlegmatic Munziq high-, medium-, and low-dose groups, 18 mice in each group. Another 18 three-month-old C57BL/6J mice were chosen as normal control group. All administration groups received relevant medicine for successive 6 months. Then the changes in ability of learning and memory of mice were detected by Step-down test; protein expressions of LRP1 and RAGE were detected by immunohistochemistry and Western blot. Results Compared with the normal control group, the reaction time of learning grades and the mistake times increased, incubation of memory grades decreased and the mistake times increased in the model control group(P<0.01); Compared with the model control group, the reaction time of learning grades and the mistake times decreased, incubation of memory grades increased and the mistake times decreased in all administration groups(P<0.05, P<0.01). Immunohistochemistry and Western blot results showed that compared with normal control group, the LRP1 expression decreased and RAGE increased in the model control group(P<0.05); Compared with the model control group, the LRP1 expression decreased and RAGE increased in Abnormal Phlegmatic Munziq high-, medium-, and low-dose groups(P<0.05,P<0.01). Conclusion Abnormal Phlegmatic Munziq can improve ability of spatial learning and memory in APP/PS1 mice and regulate the expressions of RAGE and LRP1.
Objective To investigate the effects of Abnormal Phlegmatic Munziq on ability of learning and memory, and protein expressions of brain tissue RAGE and LRP1 of APP/PS1 transgenetic mice model of AD; To discuss its mechanism of action. Methods Three-month-old APP/PS1 transgenic mice were randomly divided into 5 groups: model control group, positive control group, Abnormal Phlegmatic Munziq high-, medium-, and low-dose groups, 18 mice in each group. Another 18 three-month-old C57BL/6J mice were chosen as normal control group. All administration groups received relevant medicine for successive 6 months. Then the changes in ability of learning and memory of mice were detected by Step-down test; protein expressions of LRP1 and RAGE were detected by immunohistochemistry and Western blot. Results Compared with the normal control group, the reaction time of learning grades and the mistake times increased, incubation of memory grades decreased and the mistake times increased in the model control group(P<0.01); Compared with the model control group, the reaction time of learning grades and the mistake times decreased, incubation of memory grades increased and the mistake times decreased in all administration groups(P<0.05, P<0.01). Immunohistochemistry and Western blot results showed that compared with normal control group, the LRP1 expression decreased and RAGE increased in the model control group(P<0.05); Compared with the model control group, the LRP1 expression decreased and RAGE increased in Abnormal Phlegmatic Munziq high-, medium-, and low-dose groups(P<0.05,P<0.01). Conclusion Abnormal Phlegmatic Munziq can improve ability of spatial learning and memory in APP/PS1 mice and regulate the expressions of RAGE and LRP1.
引文
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[6]塔依尔·吐尔松,买吾拉尼江·依孜布拉,买地尼也提·尼亚孜,等.异常黏液质成熟剂颗粒对APP/PS1转基因小鼠行为学和海马组织病理形态学的影响[J].中国中医药信息杂志,2016,23(4):41-44.
[7]HORI O,BRETT J,SLATTERY T,et al.The Receptor for advanced glycation end products(RAGE)is a cellular binding site for amphoterin[J].Journal of Biological Chemistry,1995,270(43):25752-25761.
[8]JENNIFER W,JILL G,MPHIL K,et al.Genetic aspects of Alzheimer disease[J].Neurologist,2009,15(2):80-86.
[9]OANA C,LUCIAN H,MARIUS M,et al.Cognitive-enhancing and antioxidant activities of inhaled coriander volatile oil in amyloidβ(1-42)rat model of Alzheimer's disease[J].Physiology&Behavior,2013,120(15):193-202.
[2]MA L,CARTER R J,MORTON A J,et al.RAGE is expressed in pyramidal cells of the hippocampus following moderate hypoxic-ischemic brain injury in rats[J].Brain Res,2003,966(2):167-174.
[3]DEANE R,WU Z,SAGARE A,et a1.LRP1/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms[J].Neuron,2004,43(3):333-344.
[4]JAEGER L B,DOHG U S,SULTANA R,et al.Lipopolysaccharide alters the blood-brain barrier transport of amyloid beta protein:a mechanism for inflammation in the progression of Alzheimer's disease[J].Brain Behav Immun,2009,23(4):507-517.
[5]BANKS W A,BURNEY B O,ROBINSON S M,et al.Effects of triglycerides,obesity,and starvation on ghrelin transport across the blood-brain barrier[J].Peptides,2008,29(11):2061-2065.
[6]塔依尔·吐尔松,买吾拉尼江·依孜布拉,买地尼也提·尼亚孜,等.异常黏液质成熟剂颗粒对APP/PS1转基因小鼠行为学和海马组织病理形态学的影响[J].中国中医药信息杂志,2016,23(4):41-44.
[7]HORI O,BRETT J,SLATTERY T,et al.The Receptor for advanced glycation end products(RAGE)is a cellular binding site for amphoterin[J].Journal of Biological Chemistry,1995,270(43):25752-25761.
[8]JENNIFER W,JILL G,MPHIL K,et al.Genetic aspects of Alzheimer disease[J].Neurologist,2009,15(2):80-86.
[9]OANA C,LUCIAN H,MARIUS M,et al.Cognitive-enhancing and antioxidant activities of inhaled coriander volatile oil in amyloidβ(1-42)rat model of Alzheimer's disease[J].Physiology&Behavior,2013,120(15):193-202.