Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
CNS Neurosci Ther. 2013 Aug;19(8):603-10. doi: 10.1111/cns.12116. Epub 2013 May 3.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and Aβ-induced neuronal damage is the major pathology of AD. There is increasing evidence that neuroinflammation induced by Aβ is also involved in the pathogenesis of AD. Fasudil is a Rho kinase inhibitor and has been reported to have neuroprotective effects. In this study, the main purpose is to investigate whether fasudil has beneficial effects on cognitive impairment and neuronal toxicity induced by Aβ.
In the present study, intracerebroventricular injection of Aβ1-42 to rats resulted in marked cognitive impairment, severe neuronal damage, as well as increased IL-1β, tumor necrosis factor alpha (TNF-α) production, and NF-κB activation. Administration of fasudil significantly ameliorated the spatial learning and memory impairment, attenuated neuronal loss, and neuronal injury induced by Aβ1-42 . In addition, fasudil inhibited IL-1β and TNF-α production and NF-κB activation in the rat brain.
Fasudil can protect against Aβ-induced hippocampal neurodegeneration by suppressing inflammatory response, suggesting that fasudil might be a promising agent for the prevention and treatment of inflammation-related diseases, such as AD.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，Aβ诱导的神经元损伤是 AD 的主要病理学特征。越来越多的证据表明，Aβ诱导的神经炎症也参与了 AD 的发病机制。法舒地尔是一种 Rho 激酶抑制剂，已被报道具有神经保护作用。在本研究中，主要目的是研究法舒地尔是否对 Aβ 诱导的认知障碍和神经元毒性具有有益作用。
在本研究中，向大鼠侧脑室注射 Aβ1-42 导致明显的认知障碍、严重的神经元损伤，以及白细胞介素 1β（IL-1β）、肿瘤坏死因子-α（TNF-α）产生增加和 NF-κB 激活。法舒地尔给药显著改善了 Aβ1-42 诱导的空间学习和记忆障碍，减轻了神经元丢失和损伤。此外，法舒地尔抑制了大鼠大脑中 IL-1β 和 TNF-α 的产生以及 NF-κB 的激活。
法舒地尔通过抑制炎症反应来防止 Aβ 诱导的海马神经退行性变，表明法舒地尔可能是预防和治疗与炎症相关的疾病（如 AD）的有希望的药物。
