试析他汀类药物对神经细胞及神经胶质细胞ABCA1基因表达影响.docVIP

试析他汀类药物对神经细胞及神经胶质细胞ABCA1基因表达影响 　【摘要】 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 transporter 1, 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(simvastatin)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%Plt;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。 【关键词】 ATP结合盒式转运体1;辛伐他汀;普伐他汀 　　ABSTRACT: 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 Plt;0.05). 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. 　　KEY WORDS: ATPbinding cassette transporter 1 (ABCA1); simvastatin; pravastatin 　　他汀类药物是临床常用的一类降血脂药物[12]，其主要成分为胆固醇合成限速酶羟甲戊二酰辅酶A(HMGCoA)还原酶的抑制剂。辛伐他汀(simvastatin)和普伐他汀(pravastatin)已广泛应用于高血脂症的临床治疗。由于该药阻断甲羟戊酸的生化途径，不但能抑制胆固醇的合成、降低血浆LDL的水平、阻止巨噬细胞向泡沫细胞的转化，而且可以显著降低因高血脂引起的动脉粥样硬化性疾病的死亡率[3]。此外，研究表明，他汀类药物还可以升高血浆高密度脂蛋白 　　(high density lipoprotein, HDL)和载脂蛋白A。 　　ATP结合盒式转运体1(A