The effect of atorvastatin on mRNA levels of inflammatory genes expression in human peripheral blood lymphocytes by DNA microarray.

The effect of atorvastatin on mRNA levels of inflammatory genes expression in human peripheral blood lymphocytes by DNA microarray.
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DNA微阵列研究阿托伐他汀对人外周血淋巴细胞炎症基因表达mRNA水平的影响。

DOI:
10.1016/j.biopha.2010.12.005
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发表时间:
2011-03
期刊:
Biomed Pharmacother
影响因子:
--
通讯作者:
Jun Zou
Jun Zou
中科院分区:
其他
文献类型:
--
作者:
Xin Jin;He Chang;Zhongquan Qi;Yan Wang;Jun Zou

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越来越多的证据表明,他汀类药物在炎症过程中的有益作用除了具有降脂活性外,还被认为通过直接抑制炎症基因的表达而发挥抗炎作用。有关他汀类药物治疗后基因表达变化的综合分析还很少。在这项研究中,为了寻找阿托伐他汀(最有效的他汀类药物之一)治疗后的新基因,我们用正常人外周血淋巴细胞(PBL)进行了DNA微阵列分析。基因表达芯片分析显示,与对照组相比,阿托伐他汀治疗后180个炎症基因的表达下调了3倍,11个炎症基因的表达发生了变化,实时定量RT-PCR证实了这一点。结果显示,阿托伐他汀可显著降低6种细胞因子(IL-6、IL-8、IL-1、PAI-1、转化生长因子-β1、转化生长因子-β2)和5种趋化因子(CCL2、CCL7、CCL13、CCL18、CXCL1)的表达。我们的结果显示,阿托伐他汀治疗后,人外周血中这些细胞因子和趋化因子的表达发生了显着变化。这些数据似乎可以作为炎症基因变化的参考数据库,其中一些可能是阿托伐他汀治疗后的新生物标志物。
Accumulating evidence indicates that beneficial effects of statins on inflammatory processes besides their lowering-lipid activities, statins are thought to exert anti-inflammatory effects via direct inhibition of inflammatory gene expressions. Little comprehensive analysis has been made of gene-expression changes after statin therapy. In this study, to search novel genes after treatment by atorvastatin (one of the most potent statins), we performed a DNA microarray analysis by using normal human peripheral blood lymphocytes (PBL). Analysis of gene expression by cDNA microarrays showed that 180 genes were downregulated 3-fold changes by atorvastatin therapy compared with controls, changes in the expression of 11 inflammatory genes, confirmed by real-time RT-PCR. The results showed that atorvastatin significantly decreased the expression of six cytokines (IL-6, IL-8, IL-1, PAI-1, TGF-β1, TGF-β2) and five chemokines (CCL2, CCL7, CCL13, CCL18, CXCL1). Our results showed the marked changes in these cytokine and chemokine expressions in human PBL by atorvastatin therapy. It seemed that these data were useful as a reference database of inflammatory gene changes, some of which may be new biomarkers follow atorvastatin treatment.
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