淫黄葛复合剂对阿尔茨海默病小鼠行为学和海马解聚素金属蛋白酶10表达的影响

马冬雪 高维娟 贺小平 许力军 刘亚磊 董贤慧

解剖学报 ›› 2020, Vol. 51 ›› Issue (6) : 821-826.

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解剖学报 ›› 2020, Vol. 51 ›› Issue (6) : 821-826. DOI: 10.16098/j.issn.0529-1356.2020.06.003
神经生物学

淫黄葛复合剂对阿尔茨海默病小鼠行为学和海马解聚素金属蛋白酶10表达的影响

  • 马冬雪1,2 高维娟2 贺小平2 许力军2 刘亚磊2 董贤慧2*
作者信息 +

Effect of Astragalus, Epimedium and Pueraria compound on Alzheimer’s disease mice behaviors and hippocampus disintegrin and metalloprotease 10 expression#br#

  • MA Dong-xue1,2 GAO Wei-juan2 HE Xiao-ping2 XU Li-jun2 LIU Ya-lei2 DONG Xian-hui2*
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文章历史 +

摘要

目的 探讨淫羊藿、黄芪、葛根有效组分复方对阿尔茨海默病(AD)模型小鼠行为学和海马CA3区解聚素金属蛋白酶10(ADAM10)表达的影响。  方法 10月的雄性APPswe/PS1dE9双转基因模型小鼠30只随机分为复方组、模型组和去铁斯诺(DFX)组,10月龄的雄性C57BL/6 J小鼠10只作为正常对照组。用药结束后,采用Morris水迷宫检测各组小鼠学习记忆能力,并于水迷宫后取出小鼠的脑组织,应用免疫荧光、Real-time PCR和Western blotting方法检测各组小鼠海马CA3区ADAM10的表达。 结果 水迷宫实验结果显示,与正常对照组小鼠相比,模型组小鼠的逃避潜伏期、游泳距离和游泳时间均明显延长(P<0.05),穿越平台区域次数和平台区域停留时间明显减少(P<0.05),首次穿越平台的逃避潜伏期明显延长(P<0.05);与模型组小鼠相比,复方组和DFX组逃避潜伏期、游泳距离和游泳时间明显缩短(P<0.05),穿越平台区域次数和平台区域停留时间明显增多(P<0.05),首次穿越平台的逃避潜伏期明显缩短;复方组和DFX组相比,逃避潜伏期、游泳距离和游泳时间及跨台次数差异无显著性 (P>0.05),穿越平台区域次数、平台区域停留时间和首次穿越平台的逃避潜伏期差异无显著性 (P>0.05)。与正常对照组小鼠相比,模型组小鼠海马CA3区ADAM10的表达增高(P<0.05);与模型组相比,复方组和DFX组小鼠海马CA3区DAM10的表达降低(P<0.05);复方组和DFX组相比,ADAM10表达水平差异无显著性 (P>0.05)。 结论 应用淫羊藿、黄芪、葛根有效组分复方可以改善APPswe/PS1dE9双转基因AD模型小鼠的学习记忆能力,其机制可能与下调ADAM10的表达减少神经元的损伤和死亡有关。

Abstract

Objective To investigate the effects of a combination of Astragalus, Epimedium and Pueraria effective extracts on behaviors and the expression of a disintegrin and metalloprotease 10 (ADAM10) in hippocampal CA3 region of APPswe/PS1dE9 double transgenic Alzheimer’s disease (AD) model mice.   Methods Thirty 10-month-old male APPswe/PS1dE9 double transgenic model mice were randomly divided into compound group, model group and the deferox (DFX) group, and 10 age-matched male C57BL/6 J mice were used as normal controls. After the medication was over, the learning and memory ability of mice in each group was measured by Morris water maze, and the brain tissue was taken out after the water maze test. The expression of ADAM10 in hippocampal CA3 region of mice in each group was detected by immunofluorescence, Real-time PCR and Western blotting.   Results Compared with the normal control group, the escape latency, the swimming distance and the swimming time of the model group mice were significantly prolonged (P<0.05),crossing-target number and target-quadrant abidance were significantly decreases (P<0.05),escape latency for first crossing the platform was significantly prolonged(P<0.05);The escape latency, swimming distance and swimming time of astragalus, epimedium and pueraria effective component compound group and DFX group were significantly shorter than those of APPswe/PS1dE9 double transgenic AD model mice (P<0.05). Crossing-target number and target-quadrant abidance were significantly prolonged (P<0.05),escape latency for first crossing the platform was significantly decreases (P<0.05);There was no significant differences in escape latency, swimming distance, swimming time and cross times between the compound group and the DFX group (P>0.05). Crossing-target number,target-quadrant abidance and escape latency for first crossing the platform wer e no significant difference. Compared with the normal control group mice, AD model group increased the expression of hippocampal CA3 area ADAM10 (P<0.05), and the expression of ADAM10 in the hippocampal CA3 region of the compound group and DFX group was lower than that of the model group (P<0.05), but there was no significant difference in the expression of ADAM10 between the compound group and the DFX group.   Conclusion The effective components of Herba Epimedii, Astragalus membranaceus and Pueraria lobata could improve the learning and memory ability of APPswe/PS1dE9 double transgenic AD model mice, and the mechanism might be related to the down-regulation of ADAM10 expression and the reduction of neuron damage and death. 

关键词

阿尔茨海默病 / 淫羊藿 / 黄芪 / 葛根 / 解聚素金属蛋白酶10 / 免疫印迹法 / APPswe/PS1dE9双转基因模型小鼠

Key words

Alzheimer’s disease / Epimedium / Astragalus / Radix puerariae / A disintegrin and metalloprotease 10 / Western blotting / APPswe/PS1dE9 double transgenic model mouse

引用本文

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马冬雪 高维娟 贺小平 许力军 刘亚磊 董贤慧. 淫黄葛复合剂对阿尔茨海默病小鼠行为学和海马解聚素金属蛋白酶10表达的影响[J]. 解剖学报. 2020, 51(6): 821-826 https://doi.org/10.16098/j.issn.0529-1356.2020.06.003
MA Dong-xue GAO Wei-juan HE Xiao-ping XU Li-jun LIU Ya-lei DONG Xian-hui. Effect of Astragalus, Epimedium and Pueraria compound on Alzheimer’s disease mice behaviors and hippocampus disintegrin and metalloprotease 10 expression#br#[J]. Acta Anatomica Sinica. 2020, 51(6): 821-826 https://doi.org/10.16098/j.issn.0529-1356.2020.06.003
中图分类号: R741    

参考文献

[]X Wang, C Wang, G Pei. α-Secretase ADAM10 physically interacts with β-secretase BACE1 in neurons and regulates CHL1 proteolysis.[J]. Journal of Molecular Cell Biology, 2018, 10(5).
[]XianHui Dong, WeiJuan Gao, WeiNa Kong, et al. Neuroprotective effect of the active components of three Chinese herbs on brain iron load in a mouse model of Alzheimer's disease[J]. Experimental and Therapeutic Medicine, 2015, 9(4):1319-1327.
[]Zhang Y, He ML. Deferoxamine enhances alternative activation of microglia and inhibits amyloid beta deposits in APP/PS1 mice[J]. Brain Res. 2017, 1677(1):86-92.
[]Wolfe M S,Xia W, Ostaszewski B L, et al.Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature, 1999, 398(6727):513-517.
[]Bilkeigorzo A. Genetic mouse models of brain ageing and Alzheimer'sdisease [J]. Pharmacol Therapeutics, 2014, 142(2): 244-257.
[]Xu J, Wang J, Wimo A, et al. The economic burden of dementia in china, 1990-2030: Implications for health policy[J]. Bull World Health Organ, 2017, 95(1):18-26.
[] 李丽琴, 彭阿香, 张弦, et al. 巴茱合剂治疗老年性痴呆肾虚髓减证36例[J]. 福建中医药, 2016(2):14-16.
[] Xian-hui Dong, Jiang-tao Bai, Wei-na Kong, et al. Effective components of Chinese herbs reduce central nervous system function decline induced by iron overload[J]. Neural Regeneration Research, 2015, 10(5): 778-785.
[]Dong X H, Gao W J, Kong W N, et al. Neuroprotective effect of the active components of three Chinese herbs on brain iron load in a mouse model of Alzheimer's disease.[J]. Experimental & Therapeutic Medicine, 2015, 9(4):1319-1327.
[]Ballard C, Gauthier S, Corbett A, et al. Alzheimer's disease.[J]. Lancet, 2011, 377(9770):1019-1031.
[] Mc Namee,David.“World Alzheimer Report 2014:dementia and risk reduction:an analysis of protective and modifiable factors,”Alzheimer,s Disease International,London,September 2014
[]Barage S H, Sonawane K D. Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer\"s disease[J]. Neuropeptides, 2015:S0143417915000657.
[]Endres K, Anders A, Kojro E, et al. Tumor necrosis factor-α converting enzyme is processed by proprotein-convertases to its mature form which is degraded upon phorbol ester stimulation[J]. European Journal of Biochemistry, 2010, 270(11):2386-2393.
[]Devi L, Ohno M. Effects of BACE1 haploinsufficiency on APP processing and Aβ concentrations in male and female 5XFAD Alzheimer mice at different disease stages[J]. Neuroscience, 2015, 307:128-137.
[]Manzine Patricia Regina, Ettcheto Miren, Cano Amanda,Busquets Oriol, et al. ADAM10 in Alzheimer's disease: Pharmacological modulation by natural compounds and its role as a peripheral marker.[J]. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie,2019,113.
[]Tackenberg C , Nitsch R M . The secreted APP ectodomain sAPPα, but not sAPPβ, protects neurons against Aβ oligomer-induced dendritic spine loss and increased tau phosphorylation[J]. Molecular Brain, 2019, 12(1).
[]Peterslibeu C, Campagna J, Mitsumori M, et al. sAβPPα is a Potent Endogenous Inhibitor of?BACE1[J]. Journal of Alzheimers Disease Jad, 2015, 47(3):545-555.
[]Barger S W , Harmon A D . Microglial activation by Alzheimer amyloid precursor protein and modulation by apolipoprotein E[J]. Nature, 1998, 388(6645):878-881.
[]Joseph J A, Carey A, Brewer G J, et al. Dopamine and Abeta-induced stress signaling and decrements in Ca2+ buffering in primary neonatal hippocampal cells are antagonized by blueberry extract[J]. Journal of Alzheimers Disease, 2007, 11(4):433-446.
[]罗小金, 林茂, 王春梅. 炎症反应在阿尔茨海默病发病机制中的研究进展[J]. 热带医学杂志, 2016(1):119-122.
Luo XJ, Lin M, Wang CM. Role and research progress of inflammation in the mechanism of Alzheimer′s disease[J].Journal of Tropical Medicine, 2016(1):119-122.

基金

淫羊藿、黄芪、葛根有效组分复方通过诱导HAMP抑制APP淀 粉样代谢通路改善阿尔茨海默病的机制研究;河北省自然科学基金;河北省教育厅青年拔尖人才项目;河北省中医药管理局课题

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