三氯化铝诱导的阿尔茨海默病大鼠的血流动力学和神经病理学分析
Hemodynamic and neuropathological analysis in rats with aluminum trichloride-induced Alzheimer's disease.
作者信息
Chen Szu-Ming, Fan Chi-Chen, Chiue Ming-Shiuan, Chou Chi, Chen Jyh-Horng, Hseu Ruey-Shyang
机构信息
Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan ; Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu, Taiwan.
Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu, Taiwan ; Department of Physiology, Mackay Memorial Hospital, Taipei, Taiwan.
出版信息
PLoS One. 2013 Dec 20;8(12):e82561. doi: 10.1371/journal.pone.0082561. eCollection 2013.
BACKGROUND AND AIMS
Hemodynamic normality is crucial to maintaining the integrity of cerebral vessels and, therefore, preserving the cognitive functions of Alzheimer's disease patients. This study investigates the implications of the hemodynamic changes and the neuropathological diversifications of AlCl3-induced AD.
METHODS
The experimental animals were 8- to 12-wk-old male Wistar rats. The rats were randomly divided into 2 groups: a control group and a (+)control group. Food intake, water intake, and weight changes were recorded daily for 22 wk. Synchronously, the regional cerebral blood flow (rCBF) of the rats with AlCl3-induced AD were measured using magnetic resonance imaging (MRI). The hemorheological parameters were analyzed using a computerized auto-rotational rheometer. The brain tissue of the subjects was analyzed using immunohistological chemical (IHC) staining to determine the beta-amyloid (Aβ) levels.
RESULTS
The results of hemodynamic analysis revealed that the whole blood viscosity (WBV), fibrinogen, plasma viscosity and RBC aggregation index (RAI) in (+)control were significantly higher than that of control group, while erythrocyte electrophoresis (EI) of whole blood in (+)control were significantly lower than that of control group. The results of acetylcholinesterase-RBC (AChE-RBC)in the (+)control group was significantly higher than that of the control group. The results also show that the reduction of rCBF in rats with AlCl3-induced AD was approximately 50% to 60% that of normal rats. IHC stain results show that significantly more Aβ plaques accumulated in the hippocampus and cortex of the (+)control than in the control group.
CONCLUSION
The results accentuate the importance of hemorheology and reinforce the specific association between hemodynamic and neuropathological changes in rats with AlCl3-induced AD. Hemorheological parameters, such as WBV and fibrinogen, and AChE-RBC were ultimately proven to be useful biomarkers of the severity and progression of AD patients. In addition, the parameters can be substituted for invasive inspection in therapeutic intervention.
背景与目的
血流动力学正常对于维持脑血管的完整性至关重要，因此对于保护阿尔茨海默病患者的认知功能也很关键。本研究调查了三氯化铝诱导的阿尔茨海默病血流动力学变化及神经病理学多样化的影响。
方法
实验动物为8至12周龄的雄性Wistar大鼠。大鼠被随机分为2组：对照组和（+）对照组。连续22周每天记录食物摄入量、饮水量和体重变化。同时，使用磁共振成像（MRI）测量三氯化铝诱导的阿尔茨海默病大鼠的局部脑血流量（rCBF）。使用电脑自动旋转流变仪分析血液流变学参数。使用免疫组织化学（IHC）染色分析受试者的脑组织以确定β-淀粉样蛋白（Aβ）水平。
结果
血流动力学分析结果显示，（+）对照组的全血粘度（WBV）、纤维蛋白原、血浆粘度和红细胞聚集指数（RAI）显著高于对照组，而（+）对照组的全血红细胞电泳（EI）显著低于对照组。（+）对照组的乙酰胆碱酯酶-红细胞（AChE-RBC）结果显著高于对照组。结果还表明，三氯化铝诱导的阿尔茨海默病大鼠的rCBF降低约为正常大鼠的50%至60%。IHC染色结果显示，（+）对照组海马和皮质中积累的Aβ斑块明显多于对照组。
结论
结果强调了血液流变学的重要性，并加强了三氯化铝诱导的阿尔茨海默病大鼠血流动力学与神经病理学变化之间的特定关联。血液流变学参数，如WBV和纤维蛋白原，以及AChE-RBC最终被证明是阿尔茨海默病患者严重程度和病情进展的有用生物标志物。此外，这些参数可在治疗干预中替代侵入性检查。
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