新型天麻素衍生物对阿尔茨海默病模型小鼠的保护作用

Protective Effect of Novel Gastrodin Derivatives on Alzheimer's Disease Model Mice

关键词:  阿尔茨海默病  β淀粉样蛋白  天麻素衍生物  记忆损伤  炎症  氧化损伤

Key words:  Alzherimer's disease  amyloid-β  gastrondin derivative  memory loss  inflammation  oxidative stress

摘要:

目的 采用双侧侧脑室注射β淀粉样蛋白的寡聚体（amyloid-β oligomers，AβOs）建立阿尔茨海默病（Alzheimer's disease，AD）小鼠模型，并研究阿魏酸、天麻素以及天麻素衍生物3种不同化合物对其保护作用。方法 C57BL/6小鼠随机分为5组，假手术组、模型组、阿魏酸组、天麻素组和天麻素衍生物组。双侧侧脑室注射AβOs建立AD模型小鼠后，连续灌胃给药14 d。采用Y迷宫试验和跳台试验检测小鼠的记忆能力；免疫荧光法检测小鼠脑内炎症细胞星形胶质细胞和小胶质细胞的表达；qRT-PCR法检测小鼠脑内肿瘤坏死因子-α、白介素-1β、线粒体超氧化物歧化酶和过氧化氢酶的mRNA水平。结果 与模型组相比，阿魏酸组、天麻素组和天麻素衍生物组能显著提高小鼠记忆能力，降低小鼠脑内炎症反应和氧化损伤，与阿魏酸组、天麻素组相比，天麻素衍生物组也有显著性差异。结论 与阿魏酸组、天麻素组相比，天麻素衍生物更能有效地对抗AβOs所致的记忆损伤、炎症反应和氧化损伤，是一种潜在的治疗AD的药物。

Abstract:

OBJECTIVE To investigate the protective effect of ferulic acid(FA), gastrodin(Gas) and gastrodin derivative(Gas-D) in an Alzheimer's disease mouse model induced by bilateral intracerebroventricular injection of amyloid-β oligomers(AβOs). METHODS C57BL/6 mice were randomly divided into 5 groups:sham group, model group, FA group, Gas group and Gas-D group. After the bilateral lateral ventricle was injected with AβOs to establish AD model mice, continuous intragastric administration for 14 d. Y maze test and step down test were used to evaluate the memory ability. The expressions of astrocytes and microglial cells were determined by immunofluorescence. The mRNA levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), superoxide dismutase 2(SOD2) and catalase(CAT) in brain of mice were measured by qRT-PCR. RESULTS Compared with model group, FA, Gas and Gas-D groups could significantly improve the ability of memory of mice, reduce the inflammation and oxidative damage of brain tissues. Furthermore, compared with FA and Gas group, Gas-D group also had significant differences. CONCLUSION Compared with FA and Gas, Gas-D is more effective to alleviate the memory loss, inflammation and oxidative damage induced by AβOs. Thus, it provides a clinic application potential of Gas-D as a therapy of AD.