Protection of Mouse Brain from Aluminum‐induced Damage by Caffeic Acid
Protection of Mouse Brain from Aluminum‐induced Damage by Caffeic Acid
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DOI：
10.1111/j.1527-3458.2007.00031.x
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发表时间：
2008-03
影响因子：
5.5
通讯作者：
Jun-qing Yang;Qi-Xin Zhou;Beibei Liu;Bai-Cheng He
中科院分区：
文献类型：
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作者：
Jun-qing Yang;Qi-Xin Zhou;Beibei Liu;Bai-Cheng He
天然产物咖啡酸是5-脂氧合酶（5-LOX）的特异性抑制剂;它还具有抗氧化和抗氧化特性。目前的研究旨在确定咖啡酸的神经保护特性是否是由于抑制5-LOX。侧脑室微量注射铝（5.0 μg/2.0 μL，1次/d，连续5d），造成小鼠脑损伤。在铝之前30分钟灌胃给予咖啡酸，每天重复，持续10天。通过观察小鼠的行为变化以及通过测量脑组织中的生化和病理变化来确定脑损伤。在脑组织中测量5-LOX蛋白和5-LOX mRNA表达水平。铝损害小鼠的学习和记忆，导致大脑中的神经元死亡，脑丙二醛水平升高，淀粉样前体蛋白（APP）、淀粉样β蛋白和5-LOX的蛋白表达增加。它还增加了小鼠脑组织中5-LOX mRNA的表达，降低了胆碱乙酰转移酶（ChAT）蛋白的表达。咖啡酸可以防止铝过载引起的脑损伤以及行为和生化变化。本研究的结果表明，5-LOX的过表达伴随着铝过载诱导的小鼠脑损伤，5-LOX的选择性抑制剂可能在治疗铝神经毒性和与神经元损伤相关的疾病中具有潜在的价值。
The natural product caffeic acid is a specific inhibitor of 5‐lipoxygenase (5‐LOX); it also possesses antioxidant and antiinflammatory properties. The current study was designed to determine whether the neuroprotective properties of caffeic acid are due to inhibition of 5‐LOX. Cerebral damage was induced in mice by intracerebroventricular microinjection of aluminum (5.0 μg aluminum in 2.0 μL, once a day, for 5 days). Caffeic acid was administered intragastrically at 30 min prior to aluminum and repeated daily for an additional 10 days. The brain injury was determined by observation of behavioral changes in mice, as well as by measuring biochemical and pathological changes in the cerebral tissue. The levels of 5‐LOX proteins and 5‐LOX mRNA expression were measured in brain tissue. Aluminum impaired learning and memory in mice produced neuronal death in hippocampi, elevated brain malondialdehyde levels, increased protein expression of amyloid precursor protein (APP), amyloid beta, and 5‐LOX. It also increased 5‐LOX mRNA expression and decreased choline acetyl transferase (ChAT) protein expression in the brain tissue of mice. Caffeic acid prevented brain damage as well as behavioral and biochemical changes caused by aluminum overload. The results of this study suggest that overexpression of 5‐LOX accompanies the cerebral injury induced by aluminum overload in mice, and that selective inhibitors of 5‐LOX may have potential value in the treatment of aluminum neurotoxicity and conceivably of diseases associated with neuronal injury.