Tian Ji-Sha, Zhai Qi-Jin, Zhao Ying, Chen Rui, Zhao Lian-Dong
Department of Neurology, Huai'an Second People's Hospital, Huaian, Jiangsu, 223002, PR China.
J Integr Neurosci. 2017;16(4):385-400. doi: 10.3233/JIN-170032.
Alzheimer's Disease (AD) is one of the commonest neural degeneration in aging population, and has become a global health challenge. 2-(2-benzofuranyl)-2-imidazoline (2-BFI) was reported to effectively improved the damage of patients with neuropathological disorders. In the present study, we investigated the effect of 2-BFI on the improvement of antioxidative, inflammation, and apoptosis in AD rats. Sprague-Dawley rats (2 months old, n=40) were used in this study and after injection of Aβ1-42 into hippocampal CA1 (Cornu Ammonis) region, the rats were given high, moderate and low dose of 2-BFI though intraperitoneal (i.p.) injection. Then spatial memory and navigation ability were analyzed by Morrize Water Maze. For the molecular testing, chemical colorimetry, ELISA and immunoblotting were performed to measure the activities of antioxidative enzymes, the abundance of immune cytokines and expression of apoptotic proteins, respectively. Hematoxylin and Eosin staining was used to analyze the pathological changes. We observed that 2-BFI significantly ameliorated the learning and memory abilities in rat models with AD by dosage treatment, as demonstrated by the shorten learning latency and greater times of travel across the platform quadrant. Additionally, reactive oxygen species (ROS) and malondialdehyde (MDA), were decreased after treatment of 2-BFI with dosage dependency, while the activities of superoxidase dismutase (SOD) and (GPX) Glutathione peroxidase were in turn enhanced, suggesting that 2-BFI could protect the antioxidative enzymes and reduce the oxidative stress in the hippocampus. Moreover, the expression of inflammatory factors including TNF-a and IL-1β were decreased after 2-BFI treatment. Additionally, the neuronal apoptosis was also attenuated, as shown by Western blot results. Taken together, the cognitive impairment in AD rats could be significantly improved by 2-BFI in a dose-dependent manner through suppressing oxidants accumulation, inhibiting of inflammatory response, as well as enhancing the neural viability.
阿尔茨海默病（AD）是老年人群中最常见的神经退行性疾病之一，已成为一项全球性的健康挑战。据报道，2-（2-苯并呋喃基）-2-咪唑啉（2-BFI）能有效改善患有神经病理学疾病患者的损伤情况。在本研究中，我们调查了2-BFI对改善AD大鼠抗氧化、炎症和凋亡方面的作用。本研究使用了40只2月龄的Sprague-Dawley大鼠，在将Aβ1-42注射到海马CA1（海马角）区域后，通过腹腔注射给予大鼠高、中、低剂量的2-BFI。然后通过Morrize水迷宫分析空间记忆和导航能力。对于分子检测，分别采用化学比色法、酶联免疫吸附测定（ELISA）和免疫印迹法来测量抗氧化酶的活性、免疫细胞因子的丰度和凋亡蛋白的表达。采用苏木精和伊红染色来分析病理变化。我们观察到，通过剂量治疗，2-BFI能显著改善AD大鼠模型的学习和记忆能力，表现为学习潜伏期缩短以及穿越平台象限的次数增加。此外，2-BFI治疗后，活性氧（ROS）和丙二醛（MDA）呈剂量依赖性降低，而超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPX）的活性则相应增强，这表明2-BFI可以保护抗氧化酶并降低海马体中的氧化应激。此外，2-BFI治疗后，包括肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）在内的炎症因子表达降低。另外，蛋白质免疫印迹结果显示神经元凋亡也得到了减轻。综上所述，2-BFI可通过抑制氧化剂积累、抑制炎症反应以及增强神经活力，以剂量依赖的方式显著改善AD大鼠的认知障碍。
