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文档分类:医学/心理学

2021年她汀类药品对神经细胞和神经胶质细胞ABCA1基因表示的影响.docx


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2021年她汀类药品对神经细胞和神经胶质细胞ABCA1基因表示的影响.docx
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她汀类药品对神经细胞和神经胶质细胞ABCA1基因表示的影响

  宫惠琳,李扩,张冠军,侯惠莲,董炜疆
  摘要 目标 观察她汀类药品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)基因表示的影响。方法 培养人类神经细胞和神经胶质细胞,分别加入不一样浓度的辛伐她汀(simvastatin)和普伐她汀(pravastatin),孵育不一样时间后分别提取细胞总RNA和胞质蛋白,RTPCR观察ABCA1基因的表示,Western blot检测ABCA1蛋白。结果 辛伐她汀和普伐她汀组显著降低了ABCA1基因和蛋白的表示,其中辛伐她汀的作用比普伐她汀显著(辛伐她汀对神经元和神经胶质细胞ABCA1基因表示分别降低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。
  关键词 ATP结合盒式转运体1;辛伐她汀;普伐她汀
  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 P<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
  她汀类药品是临床常见的一类降血脂药品[12],其关键成份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。辛伐她汀(simvastatin)和普伐她汀(pravastatin)已广泛应用于高血脂症的临床诊疗。因为该药阻断甲羟戊酸的生化路径,不仅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,而且能够显著降低因高血脂引发的动脉粥样硬化性疾病的死亡率[3]。另外,研究表明,她汀类药品还能够升高血浆高密度脂蛋白


  (high density lipoprotein, HDL)和载脂蛋白A。
  
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