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基于时间序列模型评估淀粉样蛋白引起的脑血管内皮功能损伤

朱成燕, 刘昊晨, 何华, 柳晓泉

朱成燕, 刘昊晨, 何华, 柳晓泉. 基于时间序列模型评估淀粉样蛋白引起的脑血管内皮功能损伤[J]. 中国药科大学学报, 2018, 49(4): 456-462. DOI: 10.11665/j.issn.1000-5048.20180411
引用本文: 朱成燕, 刘昊晨, 何华, 柳晓泉. 基于时间序列模型评估淀粉样蛋白引起的脑血管内皮功能损伤[J]. 中国药科大学学报, 2018, 49(4): 456-462. DOI: 10.11665/j.issn.1000-5048.20180411
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ZHU Chengyan, LIU Haochen, HE Hua, LIU Xiaoquan. Evaluating cerebral endothelial dysfunction induced by amyloid based on the time series model[J]. Journal of China Pharmaceutical University, 2018, 49(4): 456-462. DOI: 10.11665/j.issn.1000-5048.20180411
Citation: ZHU Chengyan, LIU Haochen, HE Hua, LIU Xiaoquan. Evaluating cerebral endothelial dysfunction induced by amyloid based on the time series model[J]. Journal of China Pharmaceutical University, 2018, 49(4): 456-462. DOI: 10.11665/j.issn.1000-5048.20180411
shu

基于时间序列模型评估淀粉样蛋白引起的脑血管内皮功能损伤

  • 中国药科大学药代动力学教研室

基金项目: 国家自然科学基金资助项目(No.81473274,No.81773806,No.81503145)

Evaluating cerebral endothelial dysfunction induced by amyloid based on the time series model

摘要

    摘要
  • 摘要: 建立时间序列模型评估β-淀粉样蛋白(Aβ)引起的脑血管内皮功能损伤，探讨相关标记物对脑血管内皮功能损伤的影响和贡献程度。将永生化人脑微血管内皮细胞(HCMEC/D3)与2.5 μmol/L Aβ共同孵育，在2，4，6，8，10，12，14，16，18，20，22，24 h分别测定胞浆Ca2+、线粒体膜电位(MMP)、内皮型一氧化氮合酶(eNOS)活性和细胞活力，借助时间序列模型探讨相关标记物对细胞损伤的影响和贡献程度。脉冲响应分析表明，给胞浆Ca2+一个正冲击后，细胞活力被抑制并持续走低；给eNOS和MMP一个正冲击后，细胞活力上升，并在早期上升速度较快，晚期上升速率有所下降。方差解析表明胞浆Ca2+水平在脑血管内皮细胞损伤中占主要作用，且这种影响随着疾病进程的发展而下降。结合模型研究推断在损伤早期干预Ca2+通道有可能改善Aβ引起的脑血管内皮功能损伤。
    Abstract: Time series model was developed to investigate the effect and contributions of related biomarkers on the cerebral endothelial dysfunction induced by beta amyloid(Aβ). HCMEC/D3 was incubated with 2. 5 μmol/L Aβ for 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 h, and biomarkers including cytosolic calcium ion, mitochondrial membrane potential(MMP), endothelial nitric oxide synthase(eNOS)and cell viability were determined. Time series model was established to assess the dynamic relationship between the related biomarkers and cell viability and the contribution of different biomarkers to cell damage. Impulse response analysis indicated that after a positive impact on cytosolic calcium ion, cell viability decreased and this impact continued to decline; after a positive impact on endothelial nitric oxide synthase and mitochondrial membrane potential, cell viability increases, which increased rapidly in the early stage, and the rate decreased in later stage. The result of variance decomposition showed that the cytosolic calcium ion played a major role in cerebral endothelial dysfunction induced by Aβ. Combined with the model study, it is concluded that the intervention on the level of cytosolic calcium ion at the early stage may be the possible way to slow the disease progression.
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  • [1] Chakraborty A,de Wit NM,van der Flier WM,et al.The blood brain barrier in Alzheimer′s disease[J].Vascul Pharmacol,2017,89(2017):12-18.
    [2] Gorelick PB,Scuteri A,Black SE,et al.Vascular contributions to cognitive impairment and dementia:a statement for healthcare professionals from the american heart association/american stroke association[J].Stroke,2011,42(9):2672-2713.
    [3] Guo J,Liao H.Developmet of drug for Alzheimer′s disease[J].J China Pharm Univ(中国药科大学学报),2010,41(5):395-400.
    [4] Zlokovic BV. Neurovascular pathways to neurodegeneration in Alzheimer′s disease and other disorders[J].Nat Rev Neurosci,2011,12(12):723-738.
    [5] Di Marco LY,Venneri A,Farkas E,et al.Vascular dysfunction in the pathogenesis of Alzheimer′s disease - A review of endothelium-mediated mechanisms and ensuing vicious circles[J].Neurobiol Dis,2015,82:593-606.doi: 10.1016/j.nbd.2015.08.04
    [6] Fonseca AC,Moreira PI,Oliveira CR,et al.Amyloid-beta disrupts calcium and redox homeostasis in brain endothelial cells[J].Mol Neurobiol,2015,51(2):610-622.
    [7] Toda N, Okamura T. Cerebral blood flow regulation by nitric oxide in Alzheimer′s disease[J].J Alzheimers Dis,2012,32(3):569-578.
    [8] Bose E, Hravnak M, Sereika SM. Vector autoregressive models and granger causality in time series analysis in nursing research:dynamic changes among vital signs prior to cardiorespiratory instability events as an example[J].Nurs Res,2017,66(1):12-19.
    [9] Xu B,Lin B.Assessing CO2 emissions in China′s iron and steel industry:a dynamic vector autoregression model[J].Appl Energy,2016,16:375-386.
    [10] Qin LH,Huang W,Mo XA,et al.LPS induces occludin dysregulation in cerebral microvascular endothelial cells via MAPK signaling and augmenting MMP-2 levels[J].Oxid Med Cell Longev,2015.Doi: 10.1155/2015/120641.
    [11] Certal M,Vinhas A,Pinheiro AR,et al.Calcium signaling and the novel anti-proliferative effect of the UTP-sensitive P2Y(11)receptor in rat cardiac myofibroblasts[J].Cell Calcium,2015,58(5):518-533.
    [12] Furuichi M,Yokozuka M,Takemori K,et al.The reciprocal relationship between heme oxygenase and nitric oxide synthase in the organs of lipopolysaccharide-treated rodents[J].Biomed Res,2009,30(4):235-243.
    [13] Jiang ZS,Pu ZC,Hao ZH.Carvacrol protects against spinal cord injury in rats via suppressing oxidative stress and the endothelial nitric oxide synthase pathway[J].Mol Med Rep,2015,12(4):5349-5354.
    [14] Wu J,Sun J,Xue Y.Involvement of JNK and P53 activation in G2/M cell cycle arrest and apoptosis induced by titanium dioxide nanoparticles in neuron cells[J].Toxicol Lett,2010,199(3):269-276.
    [15] Li ZH,Zhou DT.Empirical Analysis on the relationship between economic growth and environmental pollution based on VAR model-taking Shandong Province as an example[J].Enterprise Economy,2013,396(8):11-16.
    [16] Kitamura Y,Shimohama S,Kamoshima W,et al.Alteration of proteins regulating apoptosis,Bcl-2,Bcl-x,Bax,Bak,Bad,ICH-1 and CPP32 in Alzheimer′s disease[J].Brain Res,1998,780(2):260-269.
    [17] Czabotar PE,Lessene G,Strasser A,et al.Control of apoptosis by the BCL-2 protein family:implications for physiology and therapy[J].Nat Rev Mol Cell Biol,2014,15(1):49-63.
    [18] Nakagawa T,Yuan JY.Cross-talk between two cysteine protease families:activation of caspase-12 by calpain in apoptosis[J].J Cell Biol,2000,150(4):887-894.
    [19] Morishima N,Nakanishi K,Takenouchi H,et al.An endoplasmic reticulum stress-specific caspase cascade in apoptosis-cytochrome c-independent activation of caspase-9 by caspase-12[J].J Biol Chem,2002,277(37):34287-34294.
    [20] Itkin A,Dupres V,Dufrene YF,et al.Calcium ions promote formation of amyloid beta-peptide(1-40)oligomers causally implicated in neuronal toxicity of Alzheimer′s disease[J].PLoS One,2011,6(3):e18250.
    [21] Bhatia R,Lin H,Lal R.Fresh and globular amyloid beta protein(1-42)induces rapid cellular degeneration:evidence for A beta P channel-mediated cellular toxicity[J].FASEB J,2000,14(9):1233-1243.
    [22] Arispe N,Rojas E,Pollard HB.Alzheimer-disease amyloid beta-protein forms calcium channels in bilayer-membranes-blockade by tromethamine and aluminum[J].PNAS,1993,90(2):567-571.
    [23] Fonseca A,Ferreiro E,Oliveira CR,et al.Activation of the endoplasmic reticulum stress response by the amyloid-beta 1-40 peptide in brain endothelial cells[J].BBA-Mol Basis Dis,2013,1832(12):2191-2203.
    [24] Aliev G,Priyadarshini M,Reddy VP,et al.Oxidative stress mediated mitochondrial and vascular lesions as markers in the pathogenesis of Alzheimer disease[J].Curr Med Chem,2014,21(19):2208-2217.
    [25] López Arrieta JM,Birks J.Nimodipine for primary degenerative,mixed and vascular dementia[J].Cochrane Database Syst Rev,2002(3):CD000147.
    [26] Wessely P,Wober-Bingol C.Calcium channel blockers in therapy of neurologic diseases[J].Wien Med Wochenschr,1993,143(19/20):514-518.
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  • 刊出日期:  2018-08-24

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