西立伐他汀对THP-1细胞CD40和基质金属蛋白酶9表达的影响
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Effect of Cerivastatin on Expression of CD40 and Matrix Metalloproteinase-9 in THP-1 Cells
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    摘要:

    通过观察他汀类药物对单核细胞CD4 0和基质金属蛋白酶9的表达是否存在抑制作用,初步探讨他汀类药物可能的非调脂的抗动脉粥样硬化机制。将培养的THP 1细胞中加入不同浓度的西立伐他汀,运用RT PCR法检测CD4 0及基质金属蛋白酶9mRNA ,酶联免疫吸附测定法测定培养基的基质金属蛋白酶9的浓度。结果发现,西立伐他汀抑制THP 1细胞CD4 0和基质金属蛋白酶9mRNA的表达,并呈浓度依赖性。西立伐他汀在0 .0 1μmol L时,CD4 0及基质金属蛋白酶9的表达无明显降低,但在1和10 μmol L时,CD4 0mRNA的表达下调5 5 %、89% ,基质金属蛋白酶9mRNA的表达亦明显下降(0 .4 5 3±0 .13比0 .0 73±0 .0 1和0 .0 0 9±0 .0 0 1)。培养基的基质金属蛋白酶9浓度在西立伐他汀1和10 μmol L时分别从0 .4 6 9±0 .0 6降低至0 .2 4 3±0 .0 4和0 .0 39±0 .0 1(P<0 .0 5 )。结果提示,西立伐他汀能抑制THP 1细胞CD4 0表达以及基质金属蛋白酶的表达和分泌,提示他汀类药物可减轻动脉粥样斑块炎症,防止斑块破裂,从而减少急性冠状动脉事件的发生。

    Abstract:

    Aim To investigate the effects of cerivastatin on expression of matrix metalloproteinase (MMP-9) and CD40 in THP-1 cells. Methods THP-1 cells were incubated with increasing concentration of cerivastatin. MMP-9 and CD40 mRNA were detected by RT-PCR, MMP-9 concentration in media were assayed by ELISA. Results Cerivastatin inhibited the expression of CD40 and MMP-9 concentration dependently. At 0.01 μmol/L, the mRNA levels of CD40 and MMP-9 were not significantly decreased. But expression of CD40 and MMP-9 mRNA were significant down-regulated at 1 to 10 μmol/L; Level of MMP-9 concentration in media decreased from 0.469±0.06 to 0.243±0.04 and 0.039±0.01 respectively at 1 or 10 μmol/L(p<0.05). Conclusions Cerivastatin inhibited the expression of CD40 and MMP-9 in THP-1 cells, decrease the MMP-9 concentration in media, it suggest that HMG-CoA reductase inhibitors may suppress inflammatory signaling and plaque disruption which responsible for clinical acute coronary syndrome.

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李江,赵水平,彭道泉,李全忠,聂赛.西立伐他汀对THP-1细胞CD40和基质金属蛋白酶9表达的影响[J].中国动脉硬化杂志,2003,11(6):533~536.

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  • 收稿日期:2003-01-17
  • 最后修改日期:2003-06-27
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