黄连总生物碱对铝致神经元退变的保护作用  

Study on the protective effects of coptis total alkaloids on the brain damage induced by aluminium overload

作　　者：何百成[1] 滕永真[2] 杨俊卿[1] 蒋青松[1] 周岐新[1] 

机构地区：[1]重庆医科大学药理学教研室,重庆400016 [2]重庆医科大学基础医学研究所,重庆400016

出　　处：《中国药理学通报》2008年第6期800-804,共5页Chinese Pharmacological Bulletin

基　　金：重庆市自然科学基金资助项目(No048528)

摘　　要：目的采用铝负荷致小鼠脑损伤模型,探讨黄连总生物碱对铝致神经元退行性变的防治作用。方法以侧脑室注射0.25%Al溶液3μl(AlCl3.6H2O配制),以Al计算浓度,每日1次,连续5d;同时通过灌胃每日给予1次黄连总生物碱,直到实验结束(共29d)。用行为学、生物化学、免疫组织化学、等离子体原子发射光谱法和病理形态学评价小鼠的学习记忆能力、单胺氧化酶活性、线粒体铁蛋白水平、脑铁和铝水平及海马病理形态学变化。结果模型组小鼠学习记忆能力明显下降,大脑皮层、海马和纹状体MAO-B活力增加,脑铁水平明显升高,线粒体铁蛋白水平下降,而海马CA1区神经元核固缩和神经细胞丢失。黄连总生物碱(TCA)呈剂量依赖性阻遏铝负荷小鼠上述指标的改变;小檗碱和尼莫地平类也显示类似黄连总生物碱的作用。结论黄连总生物碱对铝过负荷致小鼠神经元退行性变有明显防治作用;其作用可能主要与其主要成分小檗碱有关。Aim To explore the protective effects of total coptis alkaloids （TCA）on the neurodegeneration caused by aluminium overload in mice. Methods 3 μl AlCl3 solution with the AI concentration of 0. 25% was injected into the lateral ventricle of mice once a day for 5 days. At the same time, TCA and other drugs were given through the intragastric administration （ig） once a day till the end of the experiment. The learning and memory function of mice, monoamine oxidase B （MAO-B） activity, brain iron and ferritin levels, as well as pathomorphology of hippocampi were deter- mined by means of behavioral methods, biochemstry, inductively coupled plasma atomic emission spectrome- try, radioimmunoassay, and pathomorphology, respec- tively. Results There existed decreasing learning and memory function, increasing MAO-B activity from the cortex, hippocampus, and strium, elevating brain iron and aluminum levels with diminishing ferritin level, and karyopyknosis as well as neuron loss of hippocampus in the model mice. TCA could prevent the changes above induced by aluminium overloading in a dose-dependent manner after ig administration. Similar results to coptis total alkaloids were observed when berberine or nimo- dipine was used. Conclusion TCA could alleviate the brain damage induced by aluminium overloading. This effect maybe related to berberine, the primary compo- nent of TCA.

关 键 词：铝 神经元退行性变 黄连总生物碱 小檗碱 

分 类 号：R-332[医药卫生] R284.1