N42－A对神经生长因子诱导PC12细胞分化的抑制作用

The Inhibition on NGF Induced PC12 Cell Neurite Qutgrowth by N42-A

研究表明，缺乏神经生长因子（ＮＧＦ）的营养支持是Ａｌｚｈｅｉｍｅｒ＇ｓ等神经元退行性疾病发生发展的重要原因，而ＮＧＦ和／或ＮＧＦ受体的过度表达则与一些神经系统肿瘤的发生发展有着十分密切的因果关系。采用（１２５）Ⅰ－ＮＧＦ受体特异结合实验作为ＮＧＦ受体活性物质筛选实验模型从中药牛膝中筛选出了能强烈地抑制（１２５）Ⅰ－ＮＧＦ受体结合的活性成分Ｎ４２－Ａ（ⅠＣ（５０）＝６．１８±３．４３，ｎ＝４）；细胞培养实验表明，Ｎ４２－Ａ对ＮＧＦ诱导大鼠嗜铬神经瘤ＰＣｌ２细胞的分化也具有很强的剂量依赖性抑制作用（对０．１ｎｍｏｌ／Ｌ和０．２ｎｍｏｌ／ＬＮＧＦ诱导的大鼠嗜铬神经病ＰＣ１２细胞轴突生长的半数抑制浓度分别为６μｇ／ｍＬ和２１μｇ／ｍＬ）。这表明，Ｎ４２－Ａ是神经元上介导ＮＧＦ诱导轴突生长的特异受体抑制剂，不仅对ＮＧＦ及其受体过度表达所致的神经系统肿瘤的防治具有潜在的应用价值，而且对Ａｌｚｈｅｉｍｅｒ＇ｓ等神经元退行性疾病防治药物的开发研究具有十分重要的意义。

NGF is a target-derived neuron trophic protein regulating the survival, development, and maintainence of sympathetic and some sensory neurons. It has been revealed that NGF can protect neuronal functional decay and promote nerve regenerationi NGF deficiency is the main cause of some kinds of neuron degeneration diseases such as Alzheimer' s disease,but NGF and/or its receptors overexpressed in some nerve tumors. N42-A is an antagonist of NGF receptor which can specificly inhibit NGF binding to its receptors on neuron plasma membrane (IC_(50)= 6. 18± 3. 43). In the present study, it was found that N42-A can block PC 12 cell neurite outgrowth induced by NGF; 10 μg/mL N42-A administration can obviously inhibit the neurite outgrowth. It suggests that N42-A is an antagonist of NGF receptors linked with neurite outgrowth, which makes it become important in developing drugs for tumors due to over expression of NGF and/or its receptor and diseases such as Alzheimer' s disease.