松果菊苷对低压低氧环境下小鼠空间认知功能的改善作用及机制研究
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摘要
目的:研究松果菊苷(ECH)对低压低氧环境下小鼠空间认知功能的改善作用及其作用机制。方法:将60只小鼠随机分为空白组(生理盐水)、模型组(生理盐水)、阳性组(银杏叶提取物片,100 mg/kg)和ECH低、中、高剂量组(50、75、100 mg/kg),每组10只。除空白组外,其余各组小鼠均饲养于低压氧仓模拟低压低氧,各组小鼠每天灌胃给药1次,连续给药7 d(给药后立即放入低压氧仓内);以2 min内小鼠水平与垂直活动次数为指标,评价其负面情绪与空间认知功能;苏木精-伊红染色后显微镜观察小鼠海马组织病理学变化;并检测小鼠海马组织中的超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)的水平。结果:与空白组比较,模型组小鼠水平活动次数、MDA水平均显著增加/升高(P<0.05);垂直活动次数,SOD、CAT、GSH-Px水平均显著减少/降低(P<0.05);海马组织CA1区锥体细胞排列疏松,多数锥体细胞紧缩深染。与模型组比较,阳性组和ECH高剂量组小鼠水平活动次数、MDA水平显著减少/降低(P<0.05);垂直活动次数,SOD、CAT、GSH-Px水平显著增加/升高(P<0.05);海马组织CA1区锥体细胞数量丰富,排列紧密,少量锥体细胞紧缩深染。结论:ECH对低压低氧环境下小鼠空间认知功能障碍具有一定的改善作用,其机制可能与升高海马组织中SOD、CAT、GSH-Px水平及降低MDA水平有关。
OBJECTIVE:To study the improving effects of echinacoside(ECH) on spatial cognitive function in mice under hypobaric hypoxia environment and its mechanism. METHODS:Totally 60 mice were randomly divided into blank group(normal saline),model group(normal saline),positive group(Ginkgo leaf extract tablet,100 mg/kg)and ECH low-dose,medium-dose and high-dose groups(50,75,100 mg/kg),with 10 mice in each group. Except for blank group,other groups were cultured in hypobaric oxygen chamber to simulate hypobaric hypoxia;they were given relevant medicine intragastrically once a day,for consecutive 7 d(Placing into hypobaric oxygen chamber immediately after medication). Using the times of horizontal and vertical activities of mice in 2 min as index,negative emotions and spatial cognitive function were evaluated. Histopathological changes of hippocampus in mice were observed by microscopy after HE staining. The levels of SOD, CAT, GSH-Px and MDA in hippocampal tissue of mice were detected. RESULTS:Compared with blank group,the times of horizontal activities,MDA level were increased significantly in model group(P<0.05),while the times of vertical activities,the levels of SOD,CAT and GSH-Px were decreased significantly(P<0.05);the pyramidal cells in the CA1 area of the hippocampal tissue were arranged loosely,and many pyramidal cells were compressed and stained deeply. Compared with model group,the times of horizontal activities and MDA level were decreased significantly in positive group and ECH high-dose group(P<0.05),while the times of vertical activities,the levels of SOD, CAT and GSH-Px were increased significantly(P<0.05); the pyramidal cells in the CA1 region of the hippocampal tissue were abundant and closely arranged,and a few of them are constricted and deeply stained. CONCLUSIONS:ECH can improve spatial cognitive impairment of mice under hypobaric hypoxia environment,the mechanism of which may be associated with up-regulation of SOD,CAT and GSH-Px,down-regulation of MDA in the hippocampal tissue.
OBJECTIVE:To study the improving effects of echinacoside(ECH) on spatial cognitive function in mice under hypobaric hypoxia environment and its mechanism. METHODS:Totally 60 mice were randomly divided into blank group(normal saline),model group(normal saline),positive group(Ginkgo leaf extract tablet,100 mg/kg)and ECH low-dose,medium-dose and high-dose groups(50,75,100 mg/kg),with 10 mice in each group. Except for blank group,other groups were cultured in hypobaric oxygen chamber to simulate hypobaric hypoxia;they were given relevant medicine intragastrically once a day,for consecutive 7 d(Placing into hypobaric oxygen chamber immediately after medication). Using the times of horizontal and vertical activities of mice in 2 min as index,negative emotions and spatial cognitive function were evaluated. Histopathological changes of hippocampus in mice were observed by microscopy after HE staining. The levels of SOD, CAT, GSH-Px and MDA in hippocampal tissue of mice were detected. RESULTS:Compared with blank group,the times of horizontal activities,MDA level were increased significantly in model group(P<0.05),while the times of vertical activities,the levels of SOD,CAT and GSH-Px were decreased significantly(P<0.05);the pyramidal cells in the CA1 area of the hippocampal tissue were arranged loosely,and many pyramidal cells were compressed and stained deeply. Compared with model group,the times of horizontal activities and MDA level were decreased significantly in positive group and ECH high-dose group(P<0.05),while the times of vertical activities,the levels of SOD, CAT and GSH-Px were increased significantly(P<0.05); the pyramidal cells in the CA1 region of the hippocampal tissue were abundant and closely arranged,and a few of them are constricted and deeply stained. CONCLUSIONS:ECH can improve spatial cognitive impairment of mice under hypobaric hypoxia environment,the mechanism of which may be associated with up-regulation of SOD,CAT and GSH-Px,down-regulation of MDA in the hippocampal tissue.
引文
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[14]郑伟,海军,杜立学,等.甲基莲心碱对肝缺血再灌注损伤模型小鼠氧化应激和炎症反应的影响[J].中国药房,2018,29(15):2068-2072.
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[21]林建雄,隋建峰.急性低压低氧对大鼠空间学习记忆的影响及与海马内孤啡肽的关系[J].中国应用生理学杂志,2004,20(1):12-13.
[22]SHUKITT HB,STILLMAN MJ,WELCH DI,el al.Hypobsric hypoxia impairs spatial memory in an elevationdependent fashion[J].Behav Neural Biol,1994,62(3):244-252.
[23]ABD-ELHADY RM,ELSHEIKH AM,KHALIFA AE.Anti-amnestic properties of ginkgo biloba extract on impaired memory function induced by aluminum in rats[J].Int J Dev Neurosci,2013,31(7):598-607.
[24]王晓霞,王颖超,赵明.银杏叶提取物对糖尿病外周血内皮祖细胞超氧化物歧化酶及凋亡的影响[J].医学研究生学报,2012,25(3):244-248.
[25]李洋,洪莉,刘成,等.松果菊苷药理作用研究进展[J].药学进展,2017,36(1):56-60.
[26]古力努尔·木特列夫,雷丽,屠鹏飞,等.松果菊苷抗衰老作用机制研究[J].生物物理学报,2004,20(3):183-187.
[27]刘晓明,崔晓燕,甄晓兰.黄芩提取物对阿尔茨海默病模型小鼠的抗氧化作用[J].中国药房,2015,26(19):2651-2653.
[28]CERVELLATI R,RENZULLI C,GUERRA MC,et al.Evaluation of antioxidant activity of some natural polyphenolic compounds using the briggs-rauscher reaction method[J].J Agric Food Chem,2002,50(26):7504-7509.
[29]HU C,KITTS DD.Studies on the antioxidant activity of echinacea root extract[J].J Agric Food Chem,2000,48(5):1466-1472.
[2]MAITI P,SINGH SB,MALLICK B,et al.High altitude memory impairment is due to neuronal apoptosis in hippocampus,cortex and striatum[J].J Chem Neuroanat,2008,36(4):227-238.
[3]MAITI P,MUTHURAJU S,ILAVAZHAGAN G,et al.Hypobaric hypoxia induces dendritic plasticity in cortical and hippocampal pyramidal neurons in rat brain[J].Behav Brain Res,2008,189(2):233-243.
[4]LI XH,GOU CY,YANG HS,et al.Echinacoside ameliorates D-galactosamine plus lipopolysaccharide-induced acute liver injury in mice via inhibition of apoptosis and inflammation[J].Scand J Gastroenterol,2014,49(8):993-1000.
[5]PELLATI F,BENVENUTI S,MAGRO L,et al.Analysis of phenolic compounds and radical scavenging activity of Echinacea spp.[J].J Pharm Biomed Anal,2004,35(2):289-291.
[6]DENG M,ZHAO JY,TU PF,et al.Echinacoside rescues the SHSY5Y neuronal cells from TNF alpha-induced apoptosis[J].Eur J Pharmacol,2004,505(3):11-18.
[7]GUSTAVO C.ROMAN.Facts,myths,and controversies in vascular dementia[J].J Neurol Sci,2004,226(1/2):49-52.
[8]PENG L,DAN Z,MANTIAN M,el a1.Quercetin ameliorates hypobaric hypoxia-induced memory impairment through mitochondrial and neuron function adaptation via the PGC-1-pathway[J].Restor Neurol Neurosci,2015.DOI:10.3233/RNN-140446.
[9]骆新,李建英,陶义存,等.肉苁蓉苯乙醇苷对大鼠高原脑水肿的防治作用[J].中南药学,2014,8(12):747-750.
[10]田枫,张阔,郑振辉,等.松果菊苷改善SAM-P/8小鼠学习记忆能力作用机制初探[J].实验动物科学与管理,2006,2(23):14-15.
[11]DUSEK JA,EICHENBAUM H.The hippocampus and memory for orderly stimulus relations[J].Proc Natl Acad Sci USA,1997,94(13):7109-7l14.
[12]LEVSHINA IP,MATS VN,PASIKOVA NV,et al.Comparison of the behavior of rats after immobilization with structural changes in the motor cortex[J].Neurosci Behav Physiol,2009,39(9):915-919.
[13]姚茹,张锐虎,陈朝阳,等.莲心碱对佛波酯所致耳肿胀炎症模型小鼠的抗炎作用及机制研究[J].中国药房,2018,29(17):2364-2368.
[14]郑伟,海军,杜立学,等.甲基莲心碱对肝缺血再灌注损伤模型小鼠氧化应激和炎症反应的影响[J].中国药房,2018,29(15):2068-2072.
[15]XIAO J,HUANG Y,LI X.TNP-ATP is beneficial for treatment of neonatal hypoxia-induced hypomyelination and cognitive decline[J].Neurosci Bull,2016,32(1):99-107.
[16]WEI B,LI L,HE A.Hippocampal NMDAR-WntCatenin signaling disrupted with cognitive deficits in adolescent offspring exposed to prenatal hypoxia[J].Behav Brain Res,2016.DOI:10.1016/j.brainres.2015.11.041.
[17]PAVILCEK V,SCHINLO C,NEDEL A,et al.Cognitive and emotional processing at high altitude[J].Aviat Space Environ Med,2005,76(1):28-33.
[18]MAITI P,SINGH S B,MALLICK B,et al.High altitude memory impairment is due to neuronal apoptosis in hippocampus,cortex and striatum[J].J Chem Neuroanat,2008,36(3/4):227-238.
[19]尉晓娜,谢于鹏.低氧对小鼠旷场行为的影响[J].温州医学院学报,2012,42(1):17-18.
[20]DUSEK JA,EICHENBAUM H.The hippocampus and memory for orderly stimulus relations[J].Proc Natl Acad Sci USA,1997,94(13):7109-7114.
[21]林建雄,隋建峰.急性低压低氧对大鼠空间学习记忆的影响及与海马内孤啡肽的关系[J].中国应用生理学杂志,2004,20(1):12-13.
[22]SHUKITT HB,STILLMAN MJ,WELCH DI,el al.Hypobsric hypoxia impairs spatial memory in an elevationdependent fashion[J].Behav Neural Biol,1994,62(3):244-252.
[23]ABD-ELHADY RM,ELSHEIKH AM,KHALIFA AE.Anti-amnestic properties of ginkgo biloba extract on impaired memory function induced by aluminum in rats[J].Int J Dev Neurosci,2013,31(7):598-607.
[24]王晓霞,王颖超,赵明.银杏叶提取物对糖尿病外周血内皮祖细胞超氧化物歧化酶及凋亡的影响[J].医学研究生学报,2012,25(3):244-248.
[25]李洋,洪莉,刘成,等.松果菊苷药理作用研究进展[J].药学进展,2017,36(1):56-60.
[26]古力努尔·木特列夫,雷丽,屠鹏飞,等.松果菊苷抗衰老作用机制研究[J].生物物理学报,2004,20(3):183-187.
[27]刘晓明,崔晓燕,甄晓兰.黄芩提取物对阿尔茨海默病模型小鼠的抗氧化作用[J].中国药房,2015,26(19):2651-2653.
[28]CERVELLATI R,RENZULLI C,GUERRA MC,et al.Evaluation of antioxidant activity of some natural polyphenolic compounds using the briggs-rauscher reaction method[J].J Agric Food Chem,2002,50(26):7504-7509.
[29]HU C,KITTS DD.Studies on the antioxidant activity of echinacea root extract[J].J Agric Food Chem,2000,48(5):1466-1472.