Protective effects of meloxicam on aluminum overload-induced cerebral damage in mice
Protective effects of meloxicam on aluminum overload-induced cerebral damage in mice
复制标题
美洛昔康对铝超载所致小鼠脑损伤的保护作用
DOI：
10.1016/j.ejphar.2006.07.031
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发表时间：
2006-10-10
影响因子：
5
通讯作者：
Qi-Qin, Zhou
中科院分区：
文献类型：
--
作者：
Jun-Qing, Yang;Bei-Zhong, Liu;Qi-Qin, Zhou
研究了美洛昔康对铝超载所致小鼠脑氧化损伤的保护作用。采用侧脑室注射（i. c. v.）微量注射铝（5.0 μ g/2.0 μ l），每日1次，连续5天。美洛昔康是一种选择性环氧合酶-2（考克斯-2）抑制剂，在每次铝给药前30 min灌胃（i.g），并在最后一次铝给药后连续给药10 d。在美洛昔康末次给药后2周检查行为变化，包括自发活动、被动回避和空间学习记忆能力。检测脑组织病理学改变、丙二醛含量、胆碱乙酰转移酶（ChAT）、淀粉样前体蛋白（APP）和淀粉样β蛋白的表达。此外，还检测了考克斯-2蛋白和考克斯-2 mRNA，以探讨美洛昔康的作用机制。铝负荷可引起大鼠学习记忆功能障碍。与行为学改变相一致的是，铝超负荷小鼠海马神经元死亡，丙二醛含量增加，APP、淀粉样β蛋白和考克斯-2蛋白及考克斯-2 mRNA表达增加，ChAT蛋白表达减少。美洛昔康对铝负荷引起的小鼠脑损伤及上述行为和生化改变有明显的保护作用。这些实验结果表明，考克斯-2的过度表达与铝超载引起的神经元损伤密切相关。提示选择性考克斯-2抑制剂在其他神经元损伤相关疾病的临床治疗中具有潜在的应用价值。(c)2006 Elsevier B. V.保留所有权利。
The putative protective effects of meloxicam on the oxidative damage induced by aluminum overload in mice brain were investigated. The cerebral damage model in mice was established via intracerebroventricular (i.c.v.) microinjection of aluminum (5.0 mu g in 2.0 mu l), once a day for 5 days. Meloxicam, a selective inhibitor of cyclooxygenase-2 (COX-2), was intragastrically (i.g) administered 30 min before each aluminum administration, and continuously given for another 10 days after the last aluminum administration. Behavioral changes including locomotor activity, passive avoidance, and spatial learning and memory ability were examined two weeks after the last administration of meloxicam. To determine the brain damage, we also measured pathological alterations in the cerebral tissue, malondialdehyde contents and expressions of Choline acetyltransferase (ChAT), amyloid precursor protein (APP) and amyloid beta. Furthermore, COX-2 proteins and COX-2 mRNA were examined to investigate the mechanism for underlying the effect of meloxicam. The impairment of learning and memory function was caused by aluminum overload. Consistent with the behavioral changes, neuronal death in the hippocampi, increased content of malondialdehyde, expressions of APP, amyloid beta and COX-2 proteins, as well as COX-2 mRNA, and decreased expression of ChAT protein were detected in the aluminum-overload mice. Meloxicam significantly protected mice from the brain damage, and behavioral and biochemical changes above caused by aluminum overload. These experimental results indicate that there is a close relationship between over-expression of COX-2 and neuron damage induced by aluminum overload. It also suggests that selective inhibitors of COX-2 have potential values in clinical treatment for some other neuron damage-related diseases. (c) 2006 Elsevier B.V. All rights reserved.