Fei Yu-Lang, Lv Hong-Jun, Li Yan-Bo, Liu Jie, Qian Yi-Hua, Yang Wei-Na, Ma Kai-Ge, Li Hong-Bao, Qu Qiu-Min
Department of Neurology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Department of Endocrinology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Brain Res. 2017 May 15;1663:151-160. doi: 10.1016/j.brainres.2017.03.005. Epub 2017 Mar 6.
β-Amyloid (Aβ) accumulation in the brain is the major pathophysiology of Alzheimer disease (AD). Hypertension is a risk factor for AD by promoting Aβ deposition. Traditional Chinese medicinal compound tongxinluo (TXL) can improve blood circulation and endothelium-dependent vasodilation. This study investigates the effects of TXL on cognition and Aβ using spontaneously hypertensive rats (SHRs). TXL was intragastrically administered to SHRs at low-dose, mid-dose and high-dose for 15, 30 or 60days. Cognition was evaluated with a Morris Water Maze (MWM). Aβ in the brain was detected by western blot, ELISA and Thioflavin-S staining. Western blot and RT-PCR were employed to exam the expression of receptor for advanced glycation end products (RAGE), low-density lipoprotein receptor-related protein-1 (LRP-1) and amyloid precursor protein (APP). After TXL treatment for 60days, compared with the vehicle, the number of crossed platform and the time spent in the target quadrant increased in parallel with the increasing length of treatment in MWM. Moreover, the Aβ in the hippocampus significantly decreased compared to the vehicle group, both in western blot and ELISA. Additionally, TXL reduced RAGE expression in a dose- and time-depended manner, but LRP-1 expression had no difference between TXL groups and vehicle groups. Furthermore, the β-secretase expression was significantly decreased compared to the vehicle group, but APP expression had no difference. In conclusion, TXL improved cognition and decreased Aβ in SHRs in a dose- and time-dependent manner, the underlying mechanism may involved in inhibiting RAGE and β-secretase expression.
β-淀粉样蛋白（Aβ）在大脑中的积累是阿尔茨海默病（AD）的主要病理生理学特征。高血压通过促进Aβ沉积成为AD的一个风险因素。中药复方通心络（TXL）可以改善血液循环和内皮依赖性血管舒张。本研究使用自发性高血压大鼠（SHR）探究TXL对认知和Aβ的影响。将低剂量、中剂量和高剂量的TXL灌胃给予SHR，持续15、30或60天。用莫里斯水迷宫（MWM）评估认知。通过蛋白质印迹法、酶联免疫吸附测定（ELISA）和硫黄素-S染色检测大脑中的Aβ。采用蛋白质印迹法和逆转录-聚合酶链反应（RT-PCR）检测晚期糖基化终末产物受体（RAGE）、低密度脂蛋白受体相关蛋白1（LRP-1）和淀粉样前体蛋白（APP）的表达。TXL治疗60天后，与赋形剂组相比，在MWM中穿越平台的次数和在目标象限花费的时间随着治疗时间的延长而增加。此外，蛋白质印迹法和ELISA检测均显示，与赋形剂组相比，海马体中的Aβ显著减少。此外，TXL以剂量和时间依赖性方式降低RAGE表达，但TXL组和赋形剂组之间LRP-1表达无差异。此外，与赋形剂组相比，β-分泌酶表达显著降低，但APP表达无差异。总之，TXL以剂量和时间依赖性方式改善SHR的认知并降低Aβ，其潜在机制可能与抑制RAGE和β-分泌酶表达有关。
