他汀类药物对神经细胞和神经胶质细胞ABCA1基因表达的影响

Effect of statins on ABCA1 gene expression in neurons and astrocytes

目的观察他汀类药物对神经细胞和神经胶质细胞ATP结合盒式转运体1(ATP-binding cassette transporter1,ABCA1)基因表达的影响。方法培养人类神经细胞和神经胶质细胞,分别加入不同浓度的辛伐他汀(si mvastatin)和普伐他汀(pravastatin),孵育不同时间后分别提取细胞总RNA和胞质蛋白,RT-PCR观察ABCA1基因的表达,Western blot检测ABCA1蛋白。结果辛伐他汀和普伐他汀组显著降低了ABCA1基因和蛋白的表达,其中辛伐他汀的作用比普伐他汀明显(辛伐他汀对神经元和神经胶质细胞ABCA1基因表达分别降低95%和75%P<0.05),神经元实验组比神经胶质细胞组更为敏感。结论他汀类药物可以显著降低神经元和神经胶质细胞ABCA1基因和蛋白的表达,ABCA1的降低有可能影响细胞内胆固醇的代谢,对全面评价他汀类药物对高血脂相关基因的影响及用药安全性提供了一定的实验依据。

Objective To observe the effects of statins on ATP-binding cassette transporter 1（ABCA1） gene expression in neurons and astrocytes.Methods Primary human astrocytes and neuron cell line HCN-2 were incubated with simvastatin and pravastatin at different concentrations and under different conditions.Using RNA isolated from the cultured cells,we performed quantitative PCR to measure the ABCA1 gene expression in astrocytes and neurons.The protein expression of ABCA1 was measured by Western blot.Results The two statins significantly decreased the ABCA1 gene and protein expressions.Compared with pravastatin,simvastatin significantly reduced the expression of ABCA1 in neurons and astrocytes by 95% and 75%,respectively（both P0.05）.The neurons were more sensitive than astrocytes.Conclusion The statins are capable of decreasing the ABCA1 gene and protein expressions in neurons and astrocytes,and decreased ABCA1 expression may affect cholesterol metabolism in cells.The results may provide an important experimental basis for comprehensive evaluation of the statins to treat hyperlipidemia.