尼莫地平减轻铝过负荷所致的小鼠神经元退行性变  

Nimodipine relieves neurodegeneration in mice induced by aluminum overload

作　　者：袁野[1] 杨俊卿 周岐新[1] 

机构地区：[1]重庆医科大学药学院药理学教研室,重庆400016

出　　处：《中国病理生理杂志》2011年第7期1398-1402,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30672211)

摘　　要：目的:探讨尼莫地平对铝过负荷致神经元退行性变的影响。方法:105只小鼠随机分为对照组、铝过负荷组和尼莫地平治疗组。铝过负荷组和尼莫地平治疗组以0.25%氯化铝脑室内注射2μL qd×5 d,建立铝过负荷致神经元退行性变小鼠模型;对照组注射等体积人工脑脊液。尼莫地平治疗组以尼莫地平80 mg/kg灌胃bid×30 d,对照组和铝过负荷组以等体积生理盐水灌胃bid×30 d。组织学观察神经元损伤;跳台实验检测学习记忆能力;分光光度计法检测血红素加氧酶(HO)活性;Western blotting和免疫组织化学法检测HO-1蛋白表达水平;电感耦合等离子体原子发射光谱法(ICP-AES)检测铝离子和铁离子水平。结果:与对照组相比,铝过负荷组学习记忆能力显著降低(P<0.05),神经元损伤严重,HO-1蛋白表达水平、HO活性和铁离子浓度显著升高(P<0.05);与铝过负荷组相比,尼莫地平治疗组学习记忆能力显著提高(P<0.05),神经元损伤减轻,HO-1蛋白表达水平、HO活性和铁离子浓度显著降低(P<0.05)。结论:尼莫地平可能通过抑制HO-1表达、维持铁离子稳态,减轻铝过负荷所致的神经元退行性变。AIM： To investigate the effect of nimodipine on the neurodegeneration induced by aluminum overload.METHODS： One hundred and five mice were divided into control group,aluminum overload group and aluminum overload＋nimodipine group.The mice was intracerebroventricularly injected with aluminum chloride solution（2 μL of 0.25%） once a day for 5 days to induce neurodegeneration in aluminum overload＋nimodipine group and aluminum overload group.The mice in control group were injected with artificial cerebrospinal fluid（2 μL） in the same way.Nimodipine was administered by intragastric gavage（80 mg/kg） twice a day for 30 days in aluminum overload＋nimodipine group.The normal saline was administered in the same way in control group and aluminum overload group.Histological observation was performed to evaluate the neural damage.The ability of learning and memory was detected by step-down test.Heme oxygenase（HO） activity was measured by spectrophotometer.The expression of HO-1 was determined by Western blotting and immunohistochemistry.The levels of aluminum and iron were examined by inductively coupled plasma-atomic emission spectrometry（ICP-AES）.RESULTS： Compared with control group,the ability of learning and memory was significantly impaired（P0.05）,and neurons were seriously damaged in aluminum overload group.HO-1 protein expression,HO activity and iron level in aluminum overload group were significantly increased（P0.05）.Compared with aluminum overload group,the impaired ability of learning and memory was significantly improved（P0.05） and neural damage was ameliorated in aluminum overload＋nimodipine group.HO-1 protein expression,HO activity and iron level in aluminum overload＋nimodipine group were significantly decreased（P0.05）.CONCLUSION： Nimodipine relieves the neurodegeneration induced by aluminum overload through inhibiting the expression of HO-1 and keeping the homeostasis of iron.

关 键 词：铝 铁 血红素加氧酶 神经元退行性变 尼莫地平 

分 类 号：R338[医药卫生—人体生理学] R743.31[医药卫生—基础医学]