卡托普利对Aβ1-42诱导的痴呆模型大鼠记忆功能的影响
|
摘要
目的观察血管紧张素酶抑制剂(ACEI)类药物卡托普利对Aβ1-42诱导的阿尔茨海默痴呆模型大鼠的记忆能力,学习能力的影响以及相关机制的探究。方法把SD成年大鼠60只,随机分为,模型组和假手术组,其中模型组四个亚组各12只,假手术组12只。在各组鼠脑部两侧海马区注射Aβ1-42制作大鼠AD(Alzheimer disease)痴呆模型。假手术组,使用生理盐水注射到两侧海马区,作为对照。模型组为使用卡托普利按大、中、小剂量分三亚组和生理盐水亚组。假手术组不使用药物。用Morris水迷宫实验检测大鼠的学习记忆能力,检测大脑皮层和海马区的血管紧张素转化酶(ACE)、超氧化物歧化酶(SOD)、突触素(SYP)含量。结果 Aβ1-42诱导的模型组大鼠,水迷宫实验逃避潜伏期明显延长,学习记忆能力明显障碍;与模型盐水亚组相比,使用卡托普利高剂量可以使逃避潜伏期变短,穿越平台次数增加2.1倍,平台象限时间与总时间之比增加15.7%,显示改善大鼠学习记忆能力;与模型盐水亚组相比,高剂量卡托普利亚组大鼠大脑中的ACE明显增加2.9倍,SOD含量也增加28%,海马中的突触素SYP增加2.3倍,大鼠清除β淀粉蛋白能力增加,抗氧化能力增强,记忆能力增加。结论卡托普利中高剂量明显改善Aβ1-42诱导的大鼠模型的学习记忆能力,大鼠脑皮质中的ACE和SOD含量上升,海马中突触素SYP增加,记忆能力增强。
Objective Observation of angiotensin enzyme inhibitors(ACEI)drug captopril on Aβ1-42alzheimer's dementia model in rats induced by memory ability,to explore the influence of learning ability and related mechanisms.Methods The 60 adult SD rats were divided into groups of five,With model group,the groups of mouse on both sides of the hippocampus injected Aβ1-42 making AD dementia model in rats.On both sides of control,the use of saline injected into the hippocampus,a control.Model group captopril for use in large,medium and small dose of three group and use physiological saline group.Control without the use of drugs.In Morris water maze experiment testing rats learning and memory ability,testing the cerebral cortex and hippocampus angiotensin converting enzyme Superoxide Dismutase and SYP.Results Outcomes And control than Aβ1-42 rat model induced,water maze experiment to escape significantly prolong the incubation period,the ability of learning and memory.Compared with the model of saline group,captopril high doses can escape the incubation period shorten,the cross platform number increases,the platform quadrant time and the ratio of the total time extended,according to improve the ability of learning and memory in rats;Compared with the model of saline group,with captopril ACE with a significant increase in the brains of rats and SOD content increases,the hippocampus synaptic also increases,showed an increased ability toβ-amyloid protein in rats,enhanced anti-oxidationability,memory ability increase.Conclusion Captopril high dose markedly improved the rats induced by A beta 1-42 model of learning and memory ability,hippocampal synaptic SYP increase,in the cortex of rats ACE and SOD content increased;The possible mechanism of ACEI drugs outside the cerebrovascular,ACE reactivity in the brain increases,increase the removal of the amyloid beta,reduce the toxicity of amyloid beta,increased ability to remember.
Objective Observation of angiotensin enzyme inhibitors(ACEI)drug captopril on Aβ1-42alzheimer's dementia model in rats induced by memory ability,to explore the influence of learning ability and related mechanisms.Methods The 60 adult SD rats were divided into groups of five,With model group,the groups of mouse on both sides of the hippocampus injected Aβ1-42 making AD dementia model in rats.On both sides of control,the use of saline injected into the hippocampus,a control.Model group captopril for use in large,medium and small dose of three group and use physiological saline group.Control without the use of drugs.In Morris water maze experiment testing rats learning and memory ability,testing the cerebral cortex and hippocampus angiotensin converting enzyme Superoxide Dismutase and SYP.Results Outcomes And control than Aβ1-42 rat model induced,water maze experiment to escape significantly prolong the incubation period,the ability of learning and memory.Compared with the model of saline group,captopril high doses can escape the incubation period shorten,the cross platform number increases,the platform quadrant time and the ratio of the total time extended,according to improve the ability of learning and memory in rats;Compared with the model of saline group,with captopril ACE with a significant increase in the brains of rats and SOD content increases,the hippocampus synaptic also increases,showed an increased ability toβ-amyloid protein in rats,enhanced anti-oxidationability,memory ability increase.Conclusion Captopril high dose markedly improved the rats induced by A beta 1-42 model of learning and memory ability,hippocampal synaptic SYP increase,in the cortex of rats ACE and SOD content increased;The possible mechanism of ACEI drugs outside the cerebrovascular,ACE reactivity in the brain increases,increase the removal of the amyloid beta,reduce the toxicity of amyloid beta,increased ability to remember.
引文
[1]Klungel OH,Leufkens HG,van Dijk L,et al.Sources of heterogeneity in case-control studies on associations between statins,ACEinhibitors,and proton pump inhibitors and risk of pneumonia.de Groot MC[J].European journal of epidemiology,2014,29(10):767.
[2]Loftus PA,TanM,PatelG,et al.Risk factors associated with severe and recurrent angioedema:an epidemic linked to ACE-inhibitors[J].The Laryngoscope,2014,124(11):2502.
[3]金实,金华,陈瑛,等.来氟米特联合贝那普利对糖尿病肾病大鼠肾组织MCP-1表达的影响[J].中国实验诊断学,2011,5(2):798.
[4]蔺勇,张扬,张东威,等.丰富环境干预对短暂性全脑缺血大鼠学习记忆能力的影响[J].中国实验诊断学,2010,12(1):1886.
[5]Burger D,Reudelhuber T,Mahajan A,et al.Effects of a domainselective ACE inhibitor in a mouse model of chronic angiotensin II-dependent hypertension[J].Clinical science(London,England:1979),2014,127(1):57.
[6]NawazM,Arayne MS,Sultana N,et al.Investigation of interaction studies of cefpirome with ACE-inhibitors in various buffers.Spectrochimicaacta[J].Molecular and biomolecular spectroscopy,2015,137(4):1050,
[7]Wang X,Cui M,Jia J,et al.(99m)Tc-labeled-2-arylbenzoxazole derivatives as potential Aβimaging probes for single-photon emission computed tomography[J].European journal of medicinal chemistry,2015,89(7):331.
[8]Wang XQ,Xia CL,Chen SB,et al.Design,synthesis,and biological evaluation of 2-arylethenylquinoline derivatives as multifunctional agents for the treatment of Alzheimers-disease[J].Europeanjournal of medicinal chemistry,2015,89(9):349.
[9]冷闻辉,于明,陈加俊,等.MCI-186对阿尔茨海默病大鼠海马神经元细胞增殖和细胞周期的影响[J].中国实验诊断学,2011,3(1):381.
[10]El-Sayed NS,Bayan Y.Possible role of resveratrol targeting estradiol and neprilysin pathways in lipopolysaccharide model of Alzheimer disease[J].Advances in experimental medicine and biology,2015,822(5):107.
[11]Lee JS,Lee BI,Park CB,Photo-induced inhibition of Alzheimer beta-amyloid aggregation invitro by rose Bengal[J].Biomaterials,2015,38(1):43.
[12]Zhang D,Li H,Wang JB,Echinacoside inhibits amyloid fibrillization of HEWL and protects against A-beta;-induced neurotoxicity[J].International journal of biological macromolecules,2015,72(1):243.
[2]Loftus PA,TanM,PatelG,et al.Risk factors associated with severe and recurrent angioedema:an epidemic linked to ACE-inhibitors[J].The Laryngoscope,2014,124(11):2502.
[3]金实,金华,陈瑛,等.来氟米特联合贝那普利对糖尿病肾病大鼠肾组织MCP-1表达的影响[J].中国实验诊断学,2011,5(2):798.
[4]蔺勇,张扬,张东威,等.丰富环境干预对短暂性全脑缺血大鼠学习记忆能力的影响[J].中国实验诊断学,2010,12(1):1886.
[5]Burger D,Reudelhuber T,Mahajan A,et al.Effects of a domainselective ACE inhibitor in a mouse model of chronic angiotensin II-dependent hypertension[J].Clinical science(London,England:1979),2014,127(1):57.
[6]NawazM,Arayne MS,Sultana N,et al.Investigation of interaction studies of cefpirome with ACE-inhibitors in various buffers.Spectrochimicaacta[J].Molecular and biomolecular spectroscopy,2015,137(4):1050,
[7]Wang X,Cui M,Jia J,et al.(99m)Tc-labeled-2-arylbenzoxazole derivatives as potential Aβimaging probes for single-photon emission computed tomography[J].European journal of medicinal chemistry,2015,89(7):331.
[8]Wang XQ,Xia CL,Chen SB,et al.Design,synthesis,and biological evaluation of 2-arylethenylquinoline derivatives as multifunctional agents for the treatment of Alzheimers-disease[J].Europeanjournal of medicinal chemistry,2015,89(9):349.
[9]冷闻辉,于明,陈加俊,等.MCI-186对阿尔茨海默病大鼠海马神经元细胞增殖和细胞周期的影响[J].中国实验诊断学,2011,3(1):381.
[10]El-Sayed NS,Bayan Y.Possible role of resveratrol targeting estradiol and neprilysin pathways in lipopolysaccharide model of Alzheimer disease[J].Advances in experimental medicine and biology,2015,822(5):107.
[11]Lee JS,Lee BI,Park CB,Photo-induced inhibition of Alzheimer beta-amyloid aggregation invitro by rose Bengal[J].Biomaterials,2015,38(1):43.
[12]Zhang D,Li H,Wang JB,Echinacoside inhibits amyloid fibrillization of HEWL and protects against A-beta;-induced neurotoxicity[J].International journal of biological macromolecules,2015,72(1):243.