2-(2-benzofuranyl)-2-imidazoline (2-BFI) improved the impairments in AD rat models by inhibiting oxidative stress, inflammation and apoptosis
2-(2-benzofuranyl)-2-imidazoline (2-BFI) improved the impairments in AD rat models by inhibiting oxidative stress, inflammation and apoptosis
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DOI：
10.3233/jin-170032
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发表时间：
2017-01-01
影响因子：
1.8
通讯作者：
Zhao, Lian-Dong
中科院分区：
文献类型：
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作者：
Tian, Ji-Sha;Zhai, Qi-Jin;Zhao, Lian-Dong
阿尔茨海默病（AD）是老年人最常见的神经退行性疾病之一，已成为全球性的健康挑战。2-（2-苯并呋喃基）-2-咪唑啉（2- bfi）可有效改善神经病理障碍患者的损害。在本研究中，我们研究了2-BFI对AD大鼠抗氧化、炎症和细胞凋亡的改善作用。选取2月龄的Sprague-Dawley大鼠（n = 40），在海马CA1区注射A β(1-42)后，分别腹腔注射高、中、低剂量2- bfi。利用Morrize水迷宫分析小鼠的空间记忆和导航能力。分子检测分别采用化学比色法、ELISA法和免疫印迹法检测抗氧化酶活性、免疫细胞因子丰度和凋亡蛋白表达。采用苏木精、伊红染色分析病理变化。我们观察到，通过剂量处理，2-BFI显著改善了AD模型大鼠的学习和记忆能力，表现为学习潜伏期缩短，平台象限的行走时间增加。2-BFI处理海马后，活性氧（ROS）和丙二醛（MDA）呈剂量依赖性降低，超氧化酶歧化酶（SOD）和谷胱甘肽过氧化物酶（GPX）活性增强，提示2-BFI对海马抗氧化酶具有保护作用，可减轻海马氧化应激。此外，2-BFI治疗后炎症因子TNF-a、IL-1 β的表达降低。此外，Western blot结果显示，神经元凋亡也有所减弱。综上所述，2-BFI可通过抑制氧化剂积累、抑制炎症反应、增强神经活力等方式，以剂量依赖的方式显著改善AD大鼠认知功能障碍。
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 A beta(1-42) 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-1 beta 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.