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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
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

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

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: 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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