Acetylcholinesterase inhibitors attenuate atherogenesis in apolipoprotein E-knockout mice
Acetylcholinesterase inhibitors attenuate atherogenesis in apolipoprotein E-knockout mice
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DOI：
10.1016/j.atherosclerosis.2010.07.027
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发表时间：
2010-11-01
期刊：
影响因子：
5.3
通讯作者：
Sunagawa, Kenji
中科院分区：
文献类型：
--
作者：
Inanaga, Keita;Ichiki, Toshihiro;Sunagawa, Kenji
目的：可逆性乙酰胆碱酯酶抑制剂多奈哌齐改善阿尔茨海默病患者的认知功能。据报道，胆碱能系统的刺激可改善慢性心力衰竭大鼠的长期存活，并减轻脂多糖诱导的脓毒症小鼠的炎症反应。我们试图确定多奈哌齐的胆碱能系统的药理学刺激是否减少载脂蛋白（Apo）E-敲除（KO）小鼠的动脉粥样硬化形成方法和结果：雄性ApoE-KO小鼠（10周龄）喂高脂饮食和接受血管紧张素（Ang）II（490 ng/kg/天）的输注。给予多奈哌齐或毒扁豆碱4周。口服多奈哌齐（5 mg/kg/天）或输注毒扁豆碱（2 mg/kg/天）可显著减弱动脉粥样硬化形成（油红O阳性区域），而心率、血压和总胆固醇水平无显著变化。多奈哌齐抑制单核细胞趋化蛋白-1和肿瘤坏死因子-α，NADPH氧化酶的活性和生产的活性氧species in aortico.Conclusion：本研究揭示了新的抗氧化和抗动脉粥样硬化作用的药理刺激胆碱能系统的多奈哌齐。多奈哌齐有望成为治疗动脉粥样硬化性心血管疾病的新药物。(C)2010爱思唯尔爱尔兰有限公司版权所有。
Objective: Donepezil, a reversible acetylcholinesterase inhibitor, improves cognitive function of Alzheimer's disease. Stimulation of cholinergic system was reported to improve long-term survival of rats with chronic heart failure and to attenuate inflammatory response in mice with lipopolysaccharide-induced sepsis. We sought to determine whether the pharmacological stimulation of cholinergic system by donepezil reduces atherogenesis in apolipoprotein (Apo) E-knockout (KO) mice.Methods and results: Male ApoE-KO mice (10-week-old) were fed a high-fat diet and received infusion of angiotensin (Ang) II (490 ng/kg/day). Donepezil or physostigmine was administered for 4 weeks. Oral administration of donepezil (5 mg/kg/day) or infusion of physostigmine (2 mg/kg/day) significantly attenuated atherogenesis (Oil Red O-positive area) without significant changes in heart rate, blood pressure and total cholesterol levels. Administration of donepezil suppressed expression of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha, NADPH oxidase activity and production of reactive oxygen species in the aorta.Conclusion: The present study revealed novel anti-oxidative and anti-atherosclerotic effects of pharmacological stimulation of cholinergic system by donepezil. Donepezil may be used as a novel therapeutics for the atherosclerotic cardiovascular diseases. (C) 2010 Elsevier Ireland Ltd. All rights reserved.