他汀类药物对神经细胞和神经胶质细胞ABCA1基因表(3)

2014-01-17 01:12

导读：本实验直接用神经元和神经胶质细胞作为研究对象，去除了血脑屏障的影响，从而更为直观地研究两种常用的他汀类药物对胆固醇逆向运输相关基因的影响

本实验直接用神经元和神经胶质细胞作为研究对象，去除了血脑屏障的影响，从而更为直观地研究两种常用的他汀类药物对胆固醇逆向运输相关基因的影响。实验结果显示，去除了血脑屏障对他汀类药物的影响，辛伐他汀和普伐他汀对神经元和胶质细胞的作用有很大的不同。辛伐他汀可以显著降低神经元和胶质细胞内ABCA1基因的表达，尤其是对于前者，可使ABCA1的基因表达降低约95%;而普伐他汀对两者ABCA1基因表达影响较弱。另外，加入Mevalonate后，在神经元中他汀类药物降低ABCA1基因表达的能力下降，而加入GGPP和FPP后，他汀类药物降低ABCA1基因表达的能力没有改变;在胶质细胞表现则有所不同，加入Mevalonate、GGPP和FPP后，ABCA1基因的表达几乎没有改变。以上说明了他汀类药物对神经元ABCA1基因表达的影响比对胶质细胞更为显著，并且有可能是通过减少Mevalonate的产生这一途径来实现的。研究表明，ABCA1基因可以促进胆固醇流出转运至血浆中形成新生HDL，从而使它成为降低胆固醇，防止动脉粥样硬化的重要因子。在本实验中，他汀类药物显著降低神经元和神经胶质细胞ABCA1基因的表达，对神经元和神经胶质细胞的胆固醇代谢产生严重影响，进而造成神经元和胶质细胞的变性、死亡。这是长期使用他汀类药物影响患者认知能力和记忆能力的原因之一。

　　本研究有助于更深入地了解该药物的作用机制及其不良反应，为进一步认识脂代谢异常与老年痴呆症的相互关系提供了一定的实验依据。在细胞学水平进一步证实了长期大剂量使用他汀类药物可能对神经系统造成的不良影响，提示长期服用他汀类药物的患者要特别注意用药类型、时间和用药剂量。

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